Full text data of ROCK1
ROCK1
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Rho-associated protein kinase 1; 2.7.11.1 (Renal carcinoma antigen NY-REN-35; Rho-associated, coiled-coil-containing protein kinase 1; Rho-associated, coiled-coil-containing protein kinase I; ROCK-I; p160 ROCK-1; p160ROCK)
Rho-associated protein kinase 1; 2.7.11.1 (Renal carcinoma antigen NY-REN-35; Rho-associated, coiled-coil-containing protein kinase 1; Rho-associated, coiled-coil-containing protein kinase I; ROCK-I; p160 ROCK-1; p160ROCK)
UniProt
Q13464
ID ROCK1_HUMAN Reviewed; 1354 AA.
AC Q13464; B0YJ91; Q2KHM4; Q59GZ4;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1996, sequence version 1.
DT 22-JAN-2014, entry version 145.
DE RecName: Full=Rho-associated protein kinase 1;
DE EC=2.7.11.1;
DE AltName: Full=Renal carcinoma antigen NY-REN-35;
DE AltName: Full=Rho-associated, coiled-coil-containing protein kinase 1;
DE AltName: Full=Rho-associated, coiled-coil-containing protein kinase I;
DE Short=ROCK-I;
DE AltName: Full=p160 ROCK-1;
DE Short=p160ROCK;
GN Name=ROCK1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 187-195; 281-288;
RP 465-473; 818-828; 885-893 AND 934-945, FUNCTION, PHOSPHORYLATION,
RP INTERACTION WITH RHOA, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Leukemia;
RX PubMed=8617235;
RA Ishizaki T., Maekawa M., Fujisawa K., Okawa K., Iwamatsu A.,
RA Fujita A., Watanabe N., Saito Y., Kakizuka A., Morii N., Narumiya S.;
RT "The small GTP-binding protein Rho binds to and activates a 160 kDa
RT Ser/Thr protein kinase homologous to myotonic dystrophy kinase.";
RL EMBO J. 15:1885-1893(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G;);
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 2-13; 85-94; 327-334; 405-415 AND 546-563,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Ramsay A., Leung H.Y.;
RL Submitted (MAR-2009) to UniProtKB.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 323-1027.
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP ROLE IN SMOOTH MUSCLE CONTRACTION.
RX PubMed=9722579; DOI=10.1074/jbc.273.36.23433;
RA Van Eyk J.E., Arrell D.K., Foster D.B., Strauss J.D., Heinonen T.Y.,
RA Furmaniak-Kazmierczak E., Cote G.P., Mak A.S.;
RT "Different molecular mechanisms for Rho family GTPase-dependent, Ca2+-
RT independent contraction of smooth muscle.";
RL J. Biol. Chem. 273:23433-23439(1998).
RN [7]
RP IDENTIFICATION AS A RENAL CANCER ANTIGEN.
RC TISSUE=Renal cell carcinoma;
RX PubMed=10508479;
RX DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5;
RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H.,
RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T.,
RA Old L.J.;
RT "Antigens recognized by autologous antibody in patients with renal-
RT cell carcinoma.";
RL Int. J. Cancer 83:456-464(1999).
RN [8]
RP FUNCTION, INTERACTION WITH LIMK1 AND LIMK2, AND INHIBITION BY Y-27632.
RX PubMed=10436159; DOI=10.1126/science.285.5429.895;
RA Maekawa M., Ishizaki T., Boku S., Watanabe N., Fujita A., Iwamatsu A.,
RA Obinata T., Ohashi K., Mizuno K., Narumiya S.;
RT "Signaling from Rho to the actin cytoskeleton through protein kinases
RT ROCK and LIM-kinase.";
RL Science 285:895-898(1999).
RN [9]
RP FUNCTION, AND INTERACTION WITH LIMK1.
RX PubMed=10652353; DOI=10.1074/jbc.275.5.3577;
RA Ohashi K., Nagata K., Maekawa M., Ishizaki T., Narumiya S., Mizuno K.;
RT "Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation
RT at threonine 508 within the activation loop.";
RL J. Biol. Chem. 275:3577-3582(2000).
RN [10]
RP FUNCTION, AND INTERACTION WITH LIMK2.
RX PubMed=11018042; DOI=10.1074/jbc.M007074200;
RA Sumi T., Matsumoto K., Nakamura T.;
RT "Specific activation of LIM kinase 2 via phosphorylation of threonine
RT 505 by ROCK, a Rho-dependent protein kinase.";
RL J. Biol. Chem. 276:670-676(2001).
RN [11]
RP CLEAVAGE BY CASPASE-3, MUTAGENESIS OF ASP-1113, INTERACTION WITH
RP PPP1R12A, AND FUNCTION.
RX PubMed=11283607; DOI=10.1038/35070019;
RA Sebbagh M., Renvoize C., Hamelin J., Riche N., Bertoglio J.,
RA Breard J.;
RT "Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and
RT apoptotic membrane blebbing.";
RL Nat. Cell Biol. 3:346-352(2001).
RN [12]
RP INTERACTION WITH GEM.
RX PubMed=11956230; DOI=10.1083/jcb.200111026;
RA Ward Y., Yap S.-F., Ravichandran V., Matsumura F., Ito M.,
RA Spinelli B., Kelly K.;
RT "The GTP binding proteins Gem and Rad are negative regulators of the
RT Rho-Rho kinase pathway.";
RL J. Cell Biol. 157:291-302(2002).
RN [13]
RP INTERACTION WITH RHOE AND PPP1R12A, AND SUBCELLULAR LOCATION.
RX PubMed=12773565; DOI=10.1128/MCB.23.12.4219-4229.2003;
RA Riento K., Guasch R.M., Garg R., Jin B., Ridley A.J.;
RT "RhoE binds to ROCK I and inhibits downstream signaling.";
RL Mol. Cell. Biol. 23:4219-4229(2003).
RN [14]
RP REVIEW.
RX PubMed=12778124; DOI=10.1038/nrm1128;
RA Riento K., Ridley A.J.;
RT "Rocks: multifunctional kinases in cell behaviour.";
RL Nat. Rev. Mol. Cell Biol. 4:446-456(2003).
RN [15]
RP INTERACTION WITH TSG101.
RX PubMed=17853893; DOI=10.1038/sj.emboj.7601850;
RA Morita E., Sandrin V., Chung H.Y., Morham S.G., Gygi S.P.,
RA Rodesch C.K., Sundquist W.I.;
RT "Human ESCRT and ALIX proteins interact with proteins of the midbody
RT and function in cytokinesis.";
RL EMBO J. 26:4215-4227(2007).
RN [16]
RP FUNCTION, AND INTERACTION WITH DAPK3.
RX PubMed=17158456; DOI=10.1074/jbc.M609990200;
RA Hagerty L., Weitzel D.H., Chambers J., Fortner C.N., Brush M.H.,
RA Loiselle D., Hosoya H., Haystead T.A.;
RT "ROCK1 phosphorylates and activates zipper-interacting protein
RT kinase.";
RL J. Biol. Chem. 282:4884-4893(2007).
RN [17]
RP FUNCTION, INTERACTION WITH FHOD1, AND SUBCELLULAR LOCATION.
RX PubMed=18694941; DOI=10.1074/jbc.M801800200;
RA Hannemann S., Madrid R., Stastna J., Kitzing T., Gasteier J.,
RA Schoenichen A., Bouchet J., Jimenez A., Geyer M., Grosse R.,
RA Benichou S., Fackler O.T.;
RT "The diaphanous-related formin FHOD1 associates with ROCK1 and
RT promotes Src-dependent plasma membrane blebbing.";
RL J. Biol. Chem. 283:27891-27903(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1105, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [19]
RP FUNCTION, AND INTERACTION WITH PFN1.
RX PubMed=18573880; DOI=10.1128/MCB.00079-08;
RA Shao J., Welch W.J., Diprospero N.A., Diamond M.I.;
RT "Phosphorylation of profilin by ROCK1 regulates polyglutamine
RT aggregation.";
RL Mol. Cell. Biol. 28:5196-5208(2008).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [21]
RP FUNCTION, AND INTERACTION WITH JIP3.
RX PubMed=19036714; DOI=10.1126/scisignal.1161938;
RA Ongusaha P.P., Qi H.H., Raj L., Kim Y.B., Aaronson S.A., Davis R.J.,
RA Shi Y., Liao J.K., Lee S.W.;
RT "Identification of ROCK1 as an upstream activator of the JIP-3 to JNK
RT signaling axis in response to UVB damage.";
RL Sci. Signal. 1:RA14-RA14(2008).
RN [22]
RP FUNCTION.
RX PubMed=19181962; DOI=10.1152/ajpheart.01038.2008;
RA Kroll J., Epting D., Kern K., Dietz C.T., Feng Y., Hammes H.P.,
RA Wieland T., Augustin H.G.;
RT "Inhibition of Rho-dependent kinases ROCK I/II activates VEGF-driven
RT retinal neovascularization and sprouting angiogenesis.";
RL Am. J. Physiol. 296:H893-H899(2009).
RN [23]
RP FUNCTION, AND INTERACTION WITH PPP1R12A.
RX PubMed=19131646; DOI=10.1161/CIRCRESAHA.108.188524;
RA Wang Y., Zheng X.R., Riddick N., Bryden M., Baur W., Zhang X.,
RA Surks H.K.;
RT "ROCK isoform regulation of myosin phosphatase and contractility in
RT vascular smooth muscle cells.";
RL Circ. Res. 104:531-540(2009).
RN [24]
RP FUNCTION.
RX PubMed=19997641; DOI=10.1371/journal.pone.0008190;
RA Lock F.E., Hotchin N.A.;
RT "Distinct roles for ROCK1 and ROCK2 in the regulation of keratinocyte
RT differentiation.";
RL PLoS ONE 4:E8190-E8190(2009).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1105, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-647, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [27]
RP INTERACTION WITH CHORDC1.
RX PubMed=20230755; DOI=10.1016/j.devcel.2009.12.020;
RA Ferretti R., Palumbo V., Di Savino A., Velasco S., Sbroggio M.,
RA Sportoletti P., Micale L., Turco E., Silengo L., Palumbo G.,
RA Hirsch E., Teruya-Feldstein J., Bonaccorsi S., Pandolfi P.P.,
RA Gatti M., Tarone G., Brancaccio M.;
RT "Morgana/chp-1, a ROCK inhibitor involved in centrosome duplication
RT and tumorigenesis.";
RL Dev. Cell 18:486-495(2010).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [29]
RP FUNCTION, AND CLEAVAGE BY CASPASE-3.
RX PubMed=21072057; DOI=10.1038/cdd.2010.140;
RA Gabet A.S., Coulon S., Fricot A., Vandekerckhove J., Chang Y.,
RA Ribeil J.A., Lordier L., Zermati Y., Asnafi V., Belaid Z., Debili N.,
RA Vainchenker W., Varet B., Hermine O., Courtois G.;
RT "Caspase-activated ROCK-1 allows erythroblast terminal maturation
RT independently of cytokine-induced Rho signaling.";
RL Cell Death Differ. 18:678-689(2011).
RN [30]
RP REVIEW.
RX PubMed=20803696; DOI=10.1002/cm.20472;
RA Amano M., Nakayama M., Kaibuchi K.;
RT "Rho-kinase/ROCK: A key regulator of the cytoskeleton and cell
RT polarity.";
RL Cytoskeleton 67:545-554(2010).
RN [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [32]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 947-1015 IN COMPLEX WITH
RP RHOA.
RX PubMed=14660612; DOI=10.1074/jbc.M311911200;
RA Dvorsky R., Blumenstein L., Vetter I.R., Ahmadian M.R.;
RT "Structural insights into the interaction of ROCKI with the switch
RT regions of RhoA.";
RL J. Biol. Chem. 279:7098-7104(2004).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 6-415, AND SUBUNIT.
RX PubMed=16249185; DOI=10.1074/jbc.M508847200;
RA Jacobs M., Hayakawa K., Swenson L., Bellon S., Fleming M., Taslimi P.,
RA Doran J.;
RT "The structure of dimeric ROCK I reveals the mechanism for ligand
RT selectivity.";
RL J. Biol. Chem. 281:260-268(2006).
RN [35]
RP VARIANTS [LARGE SCALE ANALYSIS] ASN-108; SER-773; PRO-1112; SER-1193;
RP GLU-1217; GLN-1262 AND ARG-1264.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Protein kinase which is a key regulator of actin
CC cytoskeleton and cell polarity. Involved in regulation of smooth
CC muscle contraction, actin cytoskeleton organization, stress fiber
CC and focal adhesion formation, neurite retraction, cell adhesion
CC and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2,
CC MYL9/MLC2, PFN1 and PPP1R12A. Phosphorylates FHOD1 and acts
CC synergistically with it to promote SRC-dependent non-apoptotic
CC plasma membrane blebbing. Phosphorylates JIP3 and regulates the
CC recruitment of JNK to JIP3 upon UVB-induced stress. Acts as a
CC suppressor of inflammatory cell migration by regulating PTEN
CC phosphorylation and stability. Acts as a negative regulator of
CC VEGF-induced angiogenic endothelial cell activation. Required for
CC centrosome positioning and centrosome-dependent exit from mitosis.
CC Plays a role in terminal erythroid differentiation. May regulate
CC closure of the eyelids and ventral body wall by inducing the
CC assembly of actomyosin bundles. Promotes keratinocyte terminal
CC differentiation. Involved in osteoblast compaction through the
CC fibronectin fibrillogenesis cell-mediated matrix assembly process,
CC essential for osteoblast mineralization.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- COFACTOR: Magnesium.
CC -!- ENZYME REGULATION: Activated by RHOA binding. Inhibited by Y-
CC 27632.
CC -!- SUBUNIT: Homodimer. Interacts with RHOB, RHOC, MYLC2B and PTEN.
CC Interacts with ITGB1BP1 (via N-terminus and PTB domain) (By
CC similarity). Interacts with RHOA (activated by GTP), CHORDC1,
CC DAPK3, GEM, JIP3, RHOE, PPP1R12A, PFN1, LIMK1, LIMK2 and TSG101.
CC Interacts with FHOD1 in a Src-dependent manner.
CC -!- INTERACTION:
CC Q13203:MYBPH; NbExp=2; IntAct=EBI-876651, EBI-5655165;
CC P61586:RHOA; NbExp=4; IntAct=EBI-876651, EBI-446668;
CC Q99816:TSG101; NbExp=4; IntAct=EBI-876651, EBI-346882;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome, centriole (By
CC similarity). Golgi apparatus membrane; Peripheral membrane
CC protein. Cell projection, bleb. Cytoplasm, cytoskeleton (By
CC similarity). Cell membrane (By similarity). Cell projection,
CC lamellipodium (By similarity). Cell projection, ruffle (By
CC similarity). Note=Associated with the mother centriole and an
CC intercentriolar linker. Colocalizes with ITGB1BP1 and ITGB1 at the
CC cell membrane predominantly in lamellipodia and membrane ruffles,
CC but also in retraction fibers. Localizes at the cell membrane in
CC an ITGB1BP1-dependent manner (By similarity). A small proportion
CC is associated with Golgi membranes.
CC -!- TISSUE SPECIFICITY: Detected in blood platelets.
CC -!- DOMAIN: The C-terminal auto-inhibitory domain interferes with
CC kinase activity. RHOA binding leads to a conformation change and
CC activation of the kinase. Truncated ROCK1 is constitutively
CC activated.
CC -!- PTM: Autophosphorylated on serine and threonine residues.
CC -!- PTM: Cleaved by caspase-3 during apoptosis. This leads to
CC constitutive activation of the kinase and membrane blebbing.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family.
CC -!- SIMILARITY: Contains 1 AGC-kinase C-terminal domain.
CC -!- SIMILARITY: Contains 1 PH domain.
CC -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- SIMILARITY: Contains 1 REM (Hr1) repeat.
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DR EMBL; U43195; AAB02814.1; -; mRNA.
DR EMBL; EF445027; ACA06069.1; -; Genomic_DNA.
DR EMBL; BC113114; AAI13115.1; -; mRNA.
DR EMBL; AB208965; BAD92202.1; -; mRNA.
DR PIR; S69211; S69211.
DR RefSeq; NP_005397.1; NM_005406.2.
DR UniGene; Hs.306307; -.
DR PDB; 1S1C; X-ray; 2.60 A; X/Y=946-1015.
DR PDB; 2ESM; X-ray; 3.20 A; A/B=6-415.
DR PDB; 2ETK; X-ray; 2.96 A; A/B=6-415.
DR PDB; 2ETR; X-ray; 2.60 A; A/B=6-415.
DR PDB; 2V55; X-ray; 3.70 A; A/C=1-406.
DR PDB; 3D9V; X-ray; 3.30 A; A/B=6-415.
DR PDB; 3NCZ; X-ray; 3.00 A; A/B/C/D=6-415.
DR PDB; 3NDM; X-ray; 3.30 A; A/B/C/D=6-415.
DR PDB; 3O0Z; X-ray; 2.33 A; A/B/C/D=535-700.
DR PDB; 3TV7; X-ray; 2.75 A; A/B/C/D=6-415.
DR PDB; 3TWJ; X-ray; 2.90 A; A/B/C/D=6-415.
DR PDB; 3V8S; X-ray; 2.29 A; A/B/C/D=6-415.
DR PDBsum; 1S1C; -.
DR PDBsum; 2ESM; -.
DR PDBsum; 2ETK; -.
DR PDBsum; 2ETR; -.
DR PDBsum; 2V55; -.
DR PDBsum; 3D9V; -.
DR PDBsum; 3NCZ; -.
DR PDBsum; 3NDM; -.
DR PDBsum; 3O0Z; -.
DR PDBsum; 3TV7; -.
DR PDBsum; 3TWJ; -.
DR PDBsum; 3V8S; -.
DR ProteinModelPortal; Q13464; -.
DR SMR; Q13464; 6-402, 535-693, 946-1014, 1119-1288.
DR IntAct; Q13464; 10.
DR MINT; MINT-1195170; -.
DR STRING; 9606.ENSP00000382697; -.
DR BindingDB; Q13464; -.
DR ChEMBL; CHEMBL3231; -.
DR GuidetoPHARMACOLOGY; 1503; -.
DR PhosphoSite; Q13464; -.
DR DMDM; 47605999; -.
DR PaxDb; Q13464; -.
DR PRIDE; Q13464; -.
DR Ensembl; ENST00000399799; ENSP00000382697; ENSG00000067900.
DR GeneID; 6093; -.
DR KEGG; hsa:6093; -.
DR UCSC; uc002kte.3; human.
DR CTD; 6093; -.
DR GeneCards; GC18M018529; -.
DR HGNC; HGNC:10251; ROCK1.
DR HPA; CAB004562; -.
DR HPA; HPA007567; -.
DR HPA; HPA045639; -.
DR MIM; 601702; gene.
DR neXtProt; NX_Q13464; -.
DR PharmGKB; PA34623; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000017259; -.
DR HOVERGEN; HBG053111; -.
DR InParanoid; Q13464; -.
DR KO; K04514; -.
DR OMA; QIEKQCS; -.
DR OrthoDB; EOG7DZ8J4; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_578; Apoptosis.
DR SignaLink; Q13464; -.
DR EvolutionaryTrace; Q13464; -.
DR GeneWiki; ROCK1; -.
DR GenomeRNAi; 6093; -.
DR NextBio; 23695; -.
DR PMAP-CutDB; B0YJ91; -.
DR PRO; PR:Q13464; -.
DR ArrayExpress; Q13464; -.
DR Bgee; Q13464; -.
DR CleanEx; HS_ROCK1; -.
DR Genevestigator; Q13464; -.
DR GO; GO:0032059; C:bleb; IEA:UniProtKB-SubCell.
DR GO; GO:0005814; C:centriole; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; TAS:ProtInc.
DR GO; GO:0003383; P:apical constriction; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0032060; P:bleb assembly; IEA:Ensembl.
DR GO; GO:0006921; P:cellular component disassembly involved in execution phase of apoptosis; TAS:Reactome.
DR GO; GO:0050901; P:leukocyte tethering or rolling; IDA:BHF-UCL.
DR GO; GO:0022614; P:membrane to membrane docking; IDA:BHF-UCL.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:2000145; P:regulation of cell motility; TAS:UniProtKB.
DR GO; GO:2000114; P:regulation of establishment of cell polarity; TAS:UniProtKB.
DR GO; GO:0051893; P:regulation of focal adhesion assembly; TAS:UniProtKB.
DR GO; GO:0045616; P:regulation of keratinocyte differentiation; IMP:UniProtKB.
DR GO; GO:0051492; P:regulation of stress fiber assembly; TAS:UniProtKB.
DR GO; GO:0007266; P:Rho protein signal transduction; TAS:ProtInc.
DR GO; GO:0006939; P:smooth muscle contraction; TAS:UniProtKB.
DR Gene3D; 2.30.29.30; -; 2.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011072; HR1_rho-bd.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR011993; PH_like_dom.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR001849; Pleckstrin_homology.
DR InterPro; IPR002219; Prot_Kinase_C-like_PE/DAG-bd.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR020684; Rho-assoc_coiled-coil_kin.
DR InterPro; IPR015008; Rho-bd_dom.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR22988:SF3; PTHR22988:SF3; 1.
DR Pfam; PF02185; HR1; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR Pfam; PF08912; Rho_Binding; 1.
DR PIRSF; PIRSF037568; Rho_kinase; 1.
DR SMART; SM00109; C1; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; FALSE_NEG.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Apoptosis; ATP-binding; Cell membrane;
KW Cell projection; Coiled coil; Complete proteome; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Golgi apparatus; Kinase;
KW Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 1354 Rho-associated protein kinase 1.
FT /FTId=PRO_0000086619.
FT DOMAIN 76 338 Protein kinase.
FT DOMAIN 341 409 AGC-kinase C-terminal.
FT REPEAT 458 542 REM.
FT DOMAIN 1118 1317 PH.
FT NP_BIND 82 90 ATP (By similarity).
FT ZN_FING 1228 1281 Phorbol-ester/DAG-type.
FT REGION 368 727 Interaction with FHOD1.
FT REGION 998 1010 RHOA binding.
FT REGION 1115 1354 Auto-inhibitory.
FT COILED 422 612 Potential.
FT COILED 1011 1102 Potential.
FT COMPBIAS 636 980 Glu-rich.
FT ACT_SITE 198 198 Proton acceptor (By similarity).
FT BINDING 105 105 ATP (By similarity).
FT SITE 1113 1114 Cleavage; by caspase-3.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 647 647 N6-acetyllysine.
FT MOD_RES 1105 1105 Phosphoserine.
FT VARIANT 108 108 S -> N (in dbSNP:rs55811609).
FT /FTId=VAR_041055.
FT VARIANT 773 773 T -> S (in dbSNP:rs45562542).
FT /FTId=VAR_041056.
FT VARIANT 1112 1112 T -> P (in dbSNP:rs35881519).
FT /FTId=VAR_041057.
FT VARIANT 1193 1193 P -> S (in a lung neuroendocrine
FT carcinoma sample; somatic mutation).
FT /FTId=VAR_041058.
FT VARIANT 1217 1217 Q -> E (in dbSNP:rs2847092).
FT /FTId=VAR_041059.
FT VARIANT 1262 1262 R -> Q (in dbSNP:rs1045142).
FT /FTId=VAR_041060.
FT VARIANT 1264 1264 C -> R (in dbSNP:rs2663698).
FT /FTId=VAR_041061.
FT MUTAGEN 1113 1113 D->A: Abolishes cleavage by caspase-3.
FT CONFLICT 170 170 V -> A (in Ref. 3; AAI13115).
FT CONFLICT 197 197 R -> G (in Ref. 3; AAI13115).
FT CONFLICT 220 220 C -> R (in Ref. 3; AAI13115).
FT CONFLICT 323 325 RLG -> GTR (in Ref. 5; BAD92202).
FT CONFLICT 521 521 D -> N (in Ref. 3; AAI13115).
FT CONFLICT 965 965 K -> R (in Ref. 3; AAI13115).
FT CONFLICT 1354 1354 S -> R (in Ref. 2; ACA06069).
FT HELIX 9 19
FT HELIX 27 41
FT HELIX 44 47
FT HELIX 50 69
FT HELIX 73 75
FT STRAND 76 84
FT STRAND 86 95
FT TURN 96 98
FT STRAND 101 108
FT HELIX 109 114
FT HELIX 121 130
FT STRAND 139 144
FT STRAND 146 153
FT STRAND 157 160
FT HELIX 161 167
FT HELIX 172 191
FT HELIX 201 203
FT STRAND 204 206
FT STRAND 212 214
FT STRAND 227 230
FT HELIX 238 240
FT HELIX 243 247
FT TURN 248 252
FT STRAND 254 256
FT HELIX 258 273
FT HELIX 283 291
FT HELIX 293 296
FT HELIX 307 316
FT HELIX 320 322
FT TURN 324 327
FT HELIX 329 333
FT HELIX 336 338
FT TURN 345 347
FT HELIX 348 350
FT HELIX 365 367
FT HELIX 392 394
FT STRAND 399 402
FT HELIX 544 691
FT HELIX 947 982
FT HELIX 984 1011
SQ SEQUENCE 1354 AA; 158175 MW; 93078CBB009A6F27 CRC64;
MSTGDSFETR FEKMDNLLRD PKSEVNSDCL LDGLDALVYD LDFPALRKNK NIDNFLSRYK
DTINKIRDLR MKAEDYEVVK VIGRGAFGEV QLVRHKSTRK VYAMKLLSKF EMIKRSDSAF
FWEERDIMAF ANSPWVVQLF YAFQDDRYLY MVMEYMPGGD LVNLMSNYDV PEKWARFYTA
EVVLALDAIH SMGFIHRDVK PDNMLLDKSG HLKLADFGTC MKMNKEGMVR CDTAVGTPDY
ISPEVLKSQG GDGYYGRECD WWSVGVFLYE MLVGDTPFYA DSLVGTYSKI MNHKNSLTFP
DDNDISKEAK NLICAFLTDR EVRLGRNGVE EIKRHLFFKN DQWAWETLRD TVAPVVPDLS
SDIDTSNFDD LEEDKGEEET FPIPKAFVGN QLPFVGFTYY SNRRYLSSAN PNDNRTSSNA
DKSLQESLQK TIYKLEEQLH NEMQLKDEME QKCRTSNIKL DKIMKELDEE GNQRRNLEST
VSQIEKEKML LQHRINEYQR KAEQENEKRR NVENEVSTLK DQLEDLKKVS QNSQLANEKL
SQLQKQLEEA NDLLRTESDT AVRLRKSHTE MSKSISQLES LNRELQERNR ILENSKSQTD
KDYYQLQAIL EAERRDRGHD SEMIGDLQAR ITSLQEEVKH LKHNLEKVEG ERKEAQDMLN
HSEKEKNNLE IDLNYKLKSL QQRLEQEVNE HKVTKARLTD KHQSIEEAKS VAMCEMEKKL
KEEREAREKA ENRVVQIEKQ CSMLDVDLKQ SQQKLEHLTG NKERMEDEVK NLTLQLEQES
NKRLLLQNEL KTQAFEADNL KGLEKQMKQE INTLLEAKRL LEFELAQLTK QYRGNEGQMR
ELQDQLEAEQ YFSTLYKTQV KELKEEIEEK NRENLKKIQE LQNEKETLAT QLDLAETKAE
SEQLARGLLE EQYFELTQES KKAASRNRQE ITDKDHTVSR LEEANSMLTK DIEILRRENE
ELTEKMKKAE EEYKLEKEEE ISNLKAAFEK NINTERTLKT QAVNKLAEIM NRKDFKIDRK
KANTQDLRKK EKENRKLQLE LNQEREKFNQ MVVKHQKELN DMQAQLVEEC AHRNELQMQL
ASKESDIEQL RAKLLDLSDS TSVASFPSAD ETDGNLPESR IEGWLSVPNR GNIKRYGWKK
QYVVVSSKKI LFYNDEQDKE QSNPSMVLDI DKLFHVRPVT QGDVYRAETE EIPKIFQILY
ANEGECRKDV EMEPVQQAEK TNFQNHKGHE FIPTLYHFPA NCDACAKPLW HVFKPPPALE
CRRCHVKCHR DHLDKKEDLI CPCKVSYDVT SARDMLLLAC SQDEQKKWVT HLVKKIPKNP
PSGFVRASPR TLSTRSTANQ SFRKVVKNTS GKTS
//
ID ROCK1_HUMAN Reviewed; 1354 AA.
AC Q13464; B0YJ91; Q2KHM4; Q59GZ4;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1996, sequence version 1.
DT 22-JAN-2014, entry version 145.
DE RecName: Full=Rho-associated protein kinase 1;
DE EC=2.7.11.1;
DE AltName: Full=Renal carcinoma antigen NY-REN-35;
DE AltName: Full=Rho-associated, coiled-coil-containing protein kinase 1;
DE AltName: Full=Rho-associated, coiled-coil-containing protein kinase I;
DE Short=ROCK-I;
DE AltName: Full=p160 ROCK-1;
DE Short=p160ROCK;
GN Name=ROCK1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 187-195; 281-288;
RP 465-473; 818-828; 885-893 AND 934-945, FUNCTION, PHOSPHORYLATION,
RP INTERACTION WITH RHOA, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Leukemia;
RX PubMed=8617235;
RA Ishizaki T., Maekawa M., Fujisawa K., Okawa K., Iwamatsu A.,
RA Fujita A., Watanabe N., Saito Y., Kakizuka A., Morii N., Narumiya S.;
RT "The small GTP-binding protein Rho binds to and activates a 160 kDa
RT Ser/Thr protein kinase homologous to myotonic dystrophy kinase.";
RL EMBO J. 15:1885-1893(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G;);
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 2-13; 85-94; 327-334; 405-415 AND 546-563,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Ramsay A., Leung H.Y.;
RL Submitted (MAR-2009) to UniProtKB.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 323-1027.
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP ROLE IN SMOOTH MUSCLE CONTRACTION.
RX PubMed=9722579; DOI=10.1074/jbc.273.36.23433;
RA Van Eyk J.E., Arrell D.K., Foster D.B., Strauss J.D., Heinonen T.Y.,
RA Furmaniak-Kazmierczak E., Cote G.P., Mak A.S.;
RT "Different molecular mechanisms for Rho family GTPase-dependent, Ca2+-
RT independent contraction of smooth muscle.";
RL J. Biol. Chem. 273:23433-23439(1998).
RN [7]
RP IDENTIFICATION AS A RENAL CANCER ANTIGEN.
RC TISSUE=Renal cell carcinoma;
RX PubMed=10508479;
RX DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5;
RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H.,
RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T.,
RA Old L.J.;
RT "Antigens recognized by autologous antibody in patients with renal-
RT cell carcinoma.";
RL Int. J. Cancer 83:456-464(1999).
RN [8]
RP FUNCTION, INTERACTION WITH LIMK1 AND LIMK2, AND INHIBITION BY Y-27632.
RX PubMed=10436159; DOI=10.1126/science.285.5429.895;
RA Maekawa M., Ishizaki T., Boku S., Watanabe N., Fujita A., Iwamatsu A.,
RA Obinata T., Ohashi K., Mizuno K., Narumiya S.;
RT "Signaling from Rho to the actin cytoskeleton through protein kinases
RT ROCK and LIM-kinase.";
RL Science 285:895-898(1999).
RN [9]
RP FUNCTION, AND INTERACTION WITH LIMK1.
RX PubMed=10652353; DOI=10.1074/jbc.275.5.3577;
RA Ohashi K., Nagata K., Maekawa M., Ishizaki T., Narumiya S., Mizuno K.;
RT "Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation
RT at threonine 508 within the activation loop.";
RL J. Biol. Chem. 275:3577-3582(2000).
RN [10]
RP FUNCTION, AND INTERACTION WITH LIMK2.
RX PubMed=11018042; DOI=10.1074/jbc.M007074200;
RA Sumi T., Matsumoto K., Nakamura T.;
RT "Specific activation of LIM kinase 2 via phosphorylation of threonine
RT 505 by ROCK, a Rho-dependent protein kinase.";
RL J. Biol. Chem. 276:670-676(2001).
RN [11]
RP CLEAVAGE BY CASPASE-3, MUTAGENESIS OF ASP-1113, INTERACTION WITH
RP PPP1R12A, AND FUNCTION.
RX PubMed=11283607; DOI=10.1038/35070019;
RA Sebbagh M., Renvoize C., Hamelin J., Riche N., Bertoglio J.,
RA Breard J.;
RT "Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and
RT apoptotic membrane blebbing.";
RL Nat. Cell Biol. 3:346-352(2001).
RN [12]
RP INTERACTION WITH GEM.
RX PubMed=11956230; DOI=10.1083/jcb.200111026;
RA Ward Y., Yap S.-F., Ravichandran V., Matsumura F., Ito M.,
RA Spinelli B., Kelly K.;
RT "The GTP binding proteins Gem and Rad are negative regulators of the
RT Rho-Rho kinase pathway.";
RL J. Cell Biol. 157:291-302(2002).
RN [13]
RP INTERACTION WITH RHOE AND PPP1R12A, AND SUBCELLULAR LOCATION.
RX PubMed=12773565; DOI=10.1128/MCB.23.12.4219-4229.2003;
RA Riento K., Guasch R.M., Garg R., Jin B., Ridley A.J.;
RT "RhoE binds to ROCK I and inhibits downstream signaling.";
RL Mol. Cell. Biol. 23:4219-4229(2003).
RN [14]
RP REVIEW.
RX PubMed=12778124; DOI=10.1038/nrm1128;
RA Riento K., Ridley A.J.;
RT "Rocks: multifunctional kinases in cell behaviour.";
RL Nat. Rev. Mol. Cell Biol. 4:446-456(2003).
RN [15]
RP INTERACTION WITH TSG101.
RX PubMed=17853893; DOI=10.1038/sj.emboj.7601850;
RA Morita E., Sandrin V., Chung H.Y., Morham S.G., Gygi S.P.,
RA Rodesch C.K., Sundquist W.I.;
RT "Human ESCRT and ALIX proteins interact with proteins of the midbody
RT and function in cytokinesis.";
RL EMBO J. 26:4215-4227(2007).
RN [16]
RP FUNCTION, AND INTERACTION WITH DAPK3.
RX PubMed=17158456; DOI=10.1074/jbc.M609990200;
RA Hagerty L., Weitzel D.H., Chambers J., Fortner C.N., Brush M.H.,
RA Loiselle D., Hosoya H., Haystead T.A.;
RT "ROCK1 phosphorylates and activates zipper-interacting protein
RT kinase.";
RL J. Biol. Chem. 282:4884-4893(2007).
RN [17]
RP FUNCTION, INTERACTION WITH FHOD1, AND SUBCELLULAR LOCATION.
RX PubMed=18694941; DOI=10.1074/jbc.M801800200;
RA Hannemann S., Madrid R., Stastna J., Kitzing T., Gasteier J.,
RA Schoenichen A., Bouchet J., Jimenez A., Geyer M., Grosse R.,
RA Benichou S., Fackler O.T.;
RT "The diaphanous-related formin FHOD1 associates with ROCK1 and
RT promotes Src-dependent plasma membrane blebbing.";
RL J. Biol. Chem. 283:27891-27903(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1105, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [19]
RP FUNCTION, AND INTERACTION WITH PFN1.
RX PubMed=18573880; DOI=10.1128/MCB.00079-08;
RA Shao J., Welch W.J., Diprospero N.A., Diamond M.I.;
RT "Phosphorylation of profilin by ROCK1 regulates polyglutamine
RT aggregation.";
RL Mol. Cell. Biol. 28:5196-5208(2008).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [21]
RP FUNCTION, AND INTERACTION WITH JIP3.
RX PubMed=19036714; DOI=10.1126/scisignal.1161938;
RA Ongusaha P.P., Qi H.H., Raj L., Kim Y.B., Aaronson S.A., Davis R.J.,
RA Shi Y., Liao J.K., Lee S.W.;
RT "Identification of ROCK1 as an upstream activator of the JIP-3 to JNK
RT signaling axis in response to UVB damage.";
RL Sci. Signal. 1:RA14-RA14(2008).
RN [22]
RP FUNCTION.
RX PubMed=19181962; DOI=10.1152/ajpheart.01038.2008;
RA Kroll J., Epting D., Kern K., Dietz C.T., Feng Y., Hammes H.P.,
RA Wieland T., Augustin H.G.;
RT "Inhibition of Rho-dependent kinases ROCK I/II activates VEGF-driven
RT retinal neovascularization and sprouting angiogenesis.";
RL Am. J. Physiol. 296:H893-H899(2009).
RN [23]
RP FUNCTION, AND INTERACTION WITH PPP1R12A.
RX PubMed=19131646; DOI=10.1161/CIRCRESAHA.108.188524;
RA Wang Y., Zheng X.R., Riddick N., Bryden M., Baur W., Zhang X.,
RA Surks H.K.;
RT "ROCK isoform regulation of myosin phosphatase and contractility in
RT vascular smooth muscle cells.";
RL Circ. Res. 104:531-540(2009).
RN [24]
RP FUNCTION.
RX PubMed=19997641; DOI=10.1371/journal.pone.0008190;
RA Lock F.E., Hotchin N.A.;
RT "Distinct roles for ROCK1 and ROCK2 in the regulation of keratinocyte
RT differentiation.";
RL PLoS ONE 4:E8190-E8190(2009).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1105, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-647, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [27]
RP INTERACTION WITH CHORDC1.
RX PubMed=20230755; DOI=10.1016/j.devcel.2009.12.020;
RA Ferretti R., Palumbo V., Di Savino A., Velasco S., Sbroggio M.,
RA Sportoletti P., Micale L., Turco E., Silengo L., Palumbo G.,
RA Hirsch E., Teruya-Feldstein J., Bonaccorsi S., Pandolfi P.P.,
RA Gatti M., Tarone G., Brancaccio M.;
RT "Morgana/chp-1, a ROCK inhibitor involved in centrosome duplication
RT and tumorigenesis.";
RL Dev. Cell 18:486-495(2010).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [29]
RP FUNCTION, AND CLEAVAGE BY CASPASE-3.
RX PubMed=21072057; DOI=10.1038/cdd.2010.140;
RA Gabet A.S., Coulon S., Fricot A., Vandekerckhove J., Chang Y.,
RA Ribeil J.A., Lordier L., Zermati Y., Asnafi V., Belaid Z., Debili N.,
RA Vainchenker W., Varet B., Hermine O., Courtois G.;
RT "Caspase-activated ROCK-1 allows erythroblast terminal maturation
RT independently of cytokine-induced Rho signaling.";
RL Cell Death Differ. 18:678-689(2011).
RN [30]
RP REVIEW.
RX PubMed=20803696; DOI=10.1002/cm.20472;
RA Amano M., Nakayama M., Kaibuchi K.;
RT "Rho-kinase/ROCK: A key regulator of the cytoskeleton and cell
RT polarity.";
RL Cytoskeleton 67:545-554(2010).
RN [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [32]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 947-1015 IN COMPLEX WITH
RP RHOA.
RX PubMed=14660612; DOI=10.1074/jbc.M311911200;
RA Dvorsky R., Blumenstein L., Vetter I.R., Ahmadian M.R.;
RT "Structural insights into the interaction of ROCKI with the switch
RT regions of RhoA.";
RL J. Biol. Chem. 279:7098-7104(2004).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 6-415, AND SUBUNIT.
RX PubMed=16249185; DOI=10.1074/jbc.M508847200;
RA Jacobs M., Hayakawa K., Swenson L., Bellon S., Fleming M., Taslimi P.,
RA Doran J.;
RT "The structure of dimeric ROCK I reveals the mechanism for ligand
RT selectivity.";
RL J. Biol. Chem. 281:260-268(2006).
RN [35]
RP VARIANTS [LARGE SCALE ANALYSIS] ASN-108; SER-773; PRO-1112; SER-1193;
RP GLU-1217; GLN-1262 AND ARG-1264.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Protein kinase which is a key regulator of actin
CC cytoskeleton and cell polarity. Involved in regulation of smooth
CC muscle contraction, actin cytoskeleton organization, stress fiber
CC and focal adhesion formation, neurite retraction, cell adhesion
CC and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2,
CC MYL9/MLC2, PFN1 and PPP1R12A. Phosphorylates FHOD1 and acts
CC synergistically with it to promote SRC-dependent non-apoptotic
CC plasma membrane blebbing. Phosphorylates JIP3 and regulates the
CC recruitment of JNK to JIP3 upon UVB-induced stress. Acts as a
CC suppressor of inflammatory cell migration by regulating PTEN
CC phosphorylation and stability. Acts as a negative regulator of
CC VEGF-induced angiogenic endothelial cell activation. Required for
CC centrosome positioning and centrosome-dependent exit from mitosis.
CC Plays a role in terminal erythroid differentiation. May regulate
CC closure of the eyelids and ventral body wall by inducing the
CC assembly of actomyosin bundles. Promotes keratinocyte terminal
CC differentiation. Involved in osteoblast compaction through the
CC fibronectin fibrillogenesis cell-mediated matrix assembly process,
CC essential for osteoblast mineralization.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- COFACTOR: Magnesium.
CC -!- ENZYME REGULATION: Activated by RHOA binding. Inhibited by Y-
CC 27632.
CC -!- SUBUNIT: Homodimer. Interacts with RHOB, RHOC, MYLC2B and PTEN.
CC Interacts with ITGB1BP1 (via N-terminus and PTB domain) (By
CC similarity). Interacts with RHOA (activated by GTP), CHORDC1,
CC DAPK3, GEM, JIP3, RHOE, PPP1R12A, PFN1, LIMK1, LIMK2 and TSG101.
CC Interacts with FHOD1 in a Src-dependent manner.
CC -!- INTERACTION:
CC Q13203:MYBPH; NbExp=2; IntAct=EBI-876651, EBI-5655165;
CC P61586:RHOA; NbExp=4; IntAct=EBI-876651, EBI-446668;
CC Q99816:TSG101; NbExp=4; IntAct=EBI-876651, EBI-346882;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome, centriole (By
CC similarity). Golgi apparatus membrane; Peripheral membrane
CC protein. Cell projection, bleb. Cytoplasm, cytoskeleton (By
CC similarity). Cell membrane (By similarity). Cell projection,
CC lamellipodium (By similarity). Cell projection, ruffle (By
CC similarity). Note=Associated with the mother centriole and an
CC intercentriolar linker. Colocalizes with ITGB1BP1 and ITGB1 at the
CC cell membrane predominantly in lamellipodia and membrane ruffles,
CC but also in retraction fibers. Localizes at the cell membrane in
CC an ITGB1BP1-dependent manner (By similarity). A small proportion
CC is associated with Golgi membranes.
CC -!- TISSUE SPECIFICITY: Detected in blood platelets.
CC -!- DOMAIN: The C-terminal auto-inhibitory domain interferes with
CC kinase activity. RHOA binding leads to a conformation change and
CC activation of the kinase. Truncated ROCK1 is constitutively
CC activated.
CC -!- PTM: Autophosphorylated on serine and threonine residues.
CC -!- PTM: Cleaved by caspase-3 during apoptosis. This leads to
CC constitutive activation of the kinase and membrane blebbing.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family.
CC -!- SIMILARITY: Contains 1 AGC-kinase C-terminal domain.
CC -!- SIMILARITY: Contains 1 PH domain.
CC -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- SIMILARITY: Contains 1 REM (Hr1) repeat.
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DR EMBL; U43195; AAB02814.1; -; mRNA.
DR EMBL; EF445027; ACA06069.1; -; Genomic_DNA.
DR EMBL; BC113114; AAI13115.1; -; mRNA.
DR EMBL; AB208965; BAD92202.1; -; mRNA.
DR PIR; S69211; S69211.
DR RefSeq; NP_005397.1; NM_005406.2.
DR UniGene; Hs.306307; -.
DR PDB; 1S1C; X-ray; 2.60 A; X/Y=946-1015.
DR PDB; 2ESM; X-ray; 3.20 A; A/B=6-415.
DR PDB; 2ETK; X-ray; 2.96 A; A/B=6-415.
DR PDB; 2ETR; X-ray; 2.60 A; A/B=6-415.
DR PDB; 2V55; X-ray; 3.70 A; A/C=1-406.
DR PDB; 3D9V; X-ray; 3.30 A; A/B=6-415.
DR PDB; 3NCZ; X-ray; 3.00 A; A/B/C/D=6-415.
DR PDB; 3NDM; X-ray; 3.30 A; A/B/C/D=6-415.
DR PDB; 3O0Z; X-ray; 2.33 A; A/B/C/D=535-700.
DR PDB; 3TV7; X-ray; 2.75 A; A/B/C/D=6-415.
DR PDB; 3TWJ; X-ray; 2.90 A; A/B/C/D=6-415.
DR PDB; 3V8S; X-ray; 2.29 A; A/B/C/D=6-415.
DR PDBsum; 1S1C; -.
DR PDBsum; 2ESM; -.
DR PDBsum; 2ETK; -.
DR PDBsum; 2ETR; -.
DR PDBsum; 2V55; -.
DR PDBsum; 3D9V; -.
DR PDBsum; 3NCZ; -.
DR PDBsum; 3NDM; -.
DR PDBsum; 3O0Z; -.
DR PDBsum; 3TV7; -.
DR PDBsum; 3TWJ; -.
DR PDBsum; 3V8S; -.
DR ProteinModelPortal; Q13464; -.
DR SMR; Q13464; 6-402, 535-693, 946-1014, 1119-1288.
DR IntAct; Q13464; 10.
DR MINT; MINT-1195170; -.
DR STRING; 9606.ENSP00000382697; -.
DR BindingDB; Q13464; -.
DR ChEMBL; CHEMBL3231; -.
DR GuidetoPHARMACOLOGY; 1503; -.
DR PhosphoSite; Q13464; -.
DR DMDM; 47605999; -.
DR PaxDb; Q13464; -.
DR PRIDE; Q13464; -.
DR Ensembl; ENST00000399799; ENSP00000382697; ENSG00000067900.
DR GeneID; 6093; -.
DR KEGG; hsa:6093; -.
DR UCSC; uc002kte.3; human.
DR CTD; 6093; -.
DR GeneCards; GC18M018529; -.
DR HGNC; HGNC:10251; ROCK1.
DR HPA; CAB004562; -.
DR HPA; HPA007567; -.
DR HPA; HPA045639; -.
DR MIM; 601702; gene.
DR neXtProt; NX_Q13464; -.
DR PharmGKB; PA34623; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000017259; -.
DR HOVERGEN; HBG053111; -.
DR InParanoid; Q13464; -.
DR KO; K04514; -.
DR OMA; QIEKQCS; -.
DR OrthoDB; EOG7DZ8J4; -.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_578; Apoptosis.
DR SignaLink; Q13464; -.
DR EvolutionaryTrace; Q13464; -.
DR GeneWiki; ROCK1; -.
DR GenomeRNAi; 6093; -.
DR NextBio; 23695; -.
DR PMAP-CutDB; B0YJ91; -.
DR PRO; PR:Q13464; -.
DR ArrayExpress; Q13464; -.
DR Bgee; Q13464; -.
DR CleanEx; HS_ROCK1; -.
DR Genevestigator; Q13464; -.
DR GO; GO:0032059; C:bleb; IEA:UniProtKB-SubCell.
DR GO; GO:0005814; C:centriole; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; TAS:ProtInc.
DR GO; GO:0003383; P:apical constriction; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0032060; P:bleb assembly; IEA:Ensembl.
DR GO; GO:0006921; P:cellular component disassembly involved in execution phase of apoptosis; TAS:Reactome.
DR GO; GO:0050901; P:leukocyte tethering or rolling; IDA:BHF-UCL.
DR GO; GO:0022614; P:membrane to membrane docking; IDA:BHF-UCL.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:2000145; P:regulation of cell motility; TAS:UniProtKB.
DR GO; GO:2000114; P:regulation of establishment of cell polarity; TAS:UniProtKB.
DR GO; GO:0051893; P:regulation of focal adhesion assembly; TAS:UniProtKB.
DR GO; GO:0045616; P:regulation of keratinocyte differentiation; IMP:UniProtKB.
DR GO; GO:0051492; P:regulation of stress fiber assembly; TAS:UniProtKB.
DR GO; GO:0007266; P:Rho protein signal transduction; TAS:ProtInc.
DR GO; GO:0006939; P:smooth muscle contraction; TAS:UniProtKB.
DR Gene3D; 2.30.29.30; -; 2.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011072; HR1_rho-bd.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR011993; PH_like_dom.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR001849; Pleckstrin_homology.
DR InterPro; IPR002219; Prot_Kinase_C-like_PE/DAG-bd.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR020684; Rho-assoc_coiled-coil_kin.
DR InterPro; IPR015008; Rho-bd_dom.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR22988:SF3; PTHR22988:SF3; 1.
DR Pfam; PF02185; HR1; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR Pfam; PF08912; Rho_Binding; 1.
DR PIRSF; PIRSF037568; Rho_kinase; 1.
DR SMART; SM00109; C1; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; FALSE_NEG.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Apoptosis; ATP-binding; Cell membrane;
KW Cell projection; Coiled coil; Complete proteome; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Golgi apparatus; Kinase;
KW Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 1354 Rho-associated protein kinase 1.
FT /FTId=PRO_0000086619.
FT DOMAIN 76 338 Protein kinase.
FT DOMAIN 341 409 AGC-kinase C-terminal.
FT REPEAT 458 542 REM.
FT DOMAIN 1118 1317 PH.
FT NP_BIND 82 90 ATP (By similarity).
FT ZN_FING 1228 1281 Phorbol-ester/DAG-type.
FT REGION 368 727 Interaction with FHOD1.
FT REGION 998 1010 RHOA binding.
FT REGION 1115 1354 Auto-inhibitory.
FT COILED 422 612 Potential.
FT COILED 1011 1102 Potential.
FT COMPBIAS 636 980 Glu-rich.
FT ACT_SITE 198 198 Proton acceptor (By similarity).
FT BINDING 105 105 ATP (By similarity).
FT SITE 1113 1114 Cleavage; by caspase-3.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 647 647 N6-acetyllysine.
FT MOD_RES 1105 1105 Phosphoserine.
FT VARIANT 108 108 S -> N (in dbSNP:rs55811609).
FT /FTId=VAR_041055.
FT VARIANT 773 773 T -> S (in dbSNP:rs45562542).
FT /FTId=VAR_041056.
FT VARIANT 1112 1112 T -> P (in dbSNP:rs35881519).
FT /FTId=VAR_041057.
FT VARIANT 1193 1193 P -> S (in a lung neuroendocrine
FT carcinoma sample; somatic mutation).
FT /FTId=VAR_041058.
FT VARIANT 1217 1217 Q -> E (in dbSNP:rs2847092).
FT /FTId=VAR_041059.
FT VARIANT 1262 1262 R -> Q (in dbSNP:rs1045142).
FT /FTId=VAR_041060.
FT VARIANT 1264 1264 C -> R (in dbSNP:rs2663698).
FT /FTId=VAR_041061.
FT MUTAGEN 1113 1113 D->A: Abolishes cleavage by caspase-3.
FT CONFLICT 170 170 V -> A (in Ref. 3; AAI13115).
FT CONFLICT 197 197 R -> G (in Ref. 3; AAI13115).
FT CONFLICT 220 220 C -> R (in Ref. 3; AAI13115).
FT CONFLICT 323 325 RLG -> GTR (in Ref. 5; BAD92202).
FT CONFLICT 521 521 D -> N (in Ref. 3; AAI13115).
FT CONFLICT 965 965 K -> R (in Ref. 3; AAI13115).
FT CONFLICT 1354 1354 S -> R (in Ref. 2; ACA06069).
FT HELIX 9 19
FT HELIX 27 41
FT HELIX 44 47
FT HELIX 50 69
FT HELIX 73 75
FT STRAND 76 84
FT STRAND 86 95
FT TURN 96 98
FT STRAND 101 108
FT HELIX 109 114
FT HELIX 121 130
FT STRAND 139 144
FT STRAND 146 153
FT STRAND 157 160
FT HELIX 161 167
FT HELIX 172 191
FT HELIX 201 203
FT STRAND 204 206
FT STRAND 212 214
FT STRAND 227 230
FT HELIX 238 240
FT HELIX 243 247
FT TURN 248 252
FT STRAND 254 256
FT HELIX 258 273
FT HELIX 283 291
FT HELIX 293 296
FT HELIX 307 316
FT HELIX 320 322
FT TURN 324 327
FT HELIX 329 333
FT HELIX 336 338
FT TURN 345 347
FT HELIX 348 350
FT HELIX 365 367
FT HELIX 392 394
FT STRAND 399 402
FT HELIX 544 691
FT HELIX 947 982
FT HELIX 984 1011
SQ SEQUENCE 1354 AA; 158175 MW; 93078CBB009A6F27 CRC64;
MSTGDSFETR FEKMDNLLRD PKSEVNSDCL LDGLDALVYD LDFPALRKNK NIDNFLSRYK
DTINKIRDLR MKAEDYEVVK VIGRGAFGEV QLVRHKSTRK VYAMKLLSKF EMIKRSDSAF
FWEERDIMAF ANSPWVVQLF YAFQDDRYLY MVMEYMPGGD LVNLMSNYDV PEKWARFYTA
EVVLALDAIH SMGFIHRDVK PDNMLLDKSG HLKLADFGTC MKMNKEGMVR CDTAVGTPDY
ISPEVLKSQG GDGYYGRECD WWSVGVFLYE MLVGDTPFYA DSLVGTYSKI MNHKNSLTFP
DDNDISKEAK NLICAFLTDR EVRLGRNGVE EIKRHLFFKN DQWAWETLRD TVAPVVPDLS
SDIDTSNFDD LEEDKGEEET FPIPKAFVGN QLPFVGFTYY SNRRYLSSAN PNDNRTSSNA
DKSLQESLQK TIYKLEEQLH NEMQLKDEME QKCRTSNIKL DKIMKELDEE GNQRRNLEST
VSQIEKEKML LQHRINEYQR KAEQENEKRR NVENEVSTLK DQLEDLKKVS QNSQLANEKL
SQLQKQLEEA NDLLRTESDT AVRLRKSHTE MSKSISQLES LNRELQERNR ILENSKSQTD
KDYYQLQAIL EAERRDRGHD SEMIGDLQAR ITSLQEEVKH LKHNLEKVEG ERKEAQDMLN
HSEKEKNNLE IDLNYKLKSL QQRLEQEVNE HKVTKARLTD KHQSIEEAKS VAMCEMEKKL
KEEREAREKA ENRVVQIEKQ CSMLDVDLKQ SQQKLEHLTG NKERMEDEVK NLTLQLEQES
NKRLLLQNEL KTQAFEADNL KGLEKQMKQE INTLLEAKRL LEFELAQLTK QYRGNEGQMR
ELQDQLEAEQ YFSTLYKTQV KELKEEIEEK NRENLKKIQE LQNEKETLAT QLDLAETKAE
SEQLARGLLE EQYFELTQES KKAASRNRQE ITDKDHTVSR LEEANSMLTK DIEILRRENE
ELTEKMKKAE EEYKLEKEEE ISNLKAAFEK NINTERTLKT QAVNKLAEIM NRKDFKIDRK
KANTQDLRKK EKENRKLQLE LNQEREKFNQ MVVKHQKELN DMQAQLVEEC AHRNELQMQL
ASKESDIEQL RAKLLDLSDS TSVASFPSAD ETDGNLPESR IEGWLSVPNR GNIKRYGWKK
QYVVVSSKKI LFYNDEQDKE QSNPSMVLDI DKLFHVRPVT QGDVYRAETE EIPKIFQILY
ANEGECRKDV EMEPVQQAEK TNFQNHKGHE FIPTLYHFPA NCDACAKPLW HVFKPPPALE
CRRCHVKCHR DHLDKKEDLI CPCKVSYDVT SARDMLLLAC SQDEQKKWVT HLVKKIPKNP
PSGFVRASPR TLSTRSTANQ SFRKVVKNTS GKTS
//
MIM
601702
*RECORD*
*FIELD* NO
601702
*FIELD* TI
*601702 RHO-ASSOCIATED COILED-COIL-CONTAINING PROTEIN KINASE 1; ROCK1
;;p160-ROCK;;
read moreRHO KINASE
*FIELD* TX
CLONING
The small GTPase Rho (165390) regulates formation of focal adhesions and
stress fibers of fibroblasts, as well as adhesion and aggregation of
platelets and lymphocytes by shuttling between the inactive GDP-bound
form and the active GTP-bound form. Rho is also essential in cytokinesis
and plays a role in transcriptional activation by serum response factor
(600589). Ishizaki et al. (1996) identified the protein serine/threonine
kinase ROCK1, which they called p160-ROCK, that is activated when bound
to the GTP-bound form of Rho. Fujisawa et al. (1996) localized the
Rho-binding domain of ROCK1 to a region between residues 934-1015.
GENE FUNCTION
Maekawa et al. (1999) demonstrated that ROCK1, a downstream effector of
Rho, phosphorylates and activates LIM kinase (see 601329) which, in
turn, phosphorylates cofilin (601442), inhibiting its
actin-depolymerizing activity. They diagrammed proposed signaling
pathways for Rho-induced remodeling of the actin cytoskeleton in their
Figure 3C.
Anderson and SundarRaj (2001) noted that increased expression of ROCK1
is associated with limbal to corneal epithelial transition on the ocular
surface. In a study of the expression of ROCK1 during the cell cycle of
the corneal epithelium, they found that levels of ROCK1 were
significantly lower in the G1 phase than in the S and G0 phases.
Downregulation of ROCK1 during the G1 phase is due in part to the
decreased levels of its mRNA. The authors concluded that ROCK1 may have
a role in the progression of the cell cycle in the corneal epithelial
cells as they migrate centripetally from the limbus across the corneal
surface.
Nakamura et al. (2001) studied the role of Rho in the migration of
corneal epithelial cells in rabbit. They detected both ROCK1 and ROCK2
(604002) in the corneal epithelium at protein and mRNA levels. They
found that exoenzyme C3, a Rho inhibitor, inhibits corneal epithelial
migration in a dose-dependent manner and prevents the stimulatory effect
of the Rho activator lysophosphatidic acid (LPA). Both cytochalasin B,
an inhibitor of actin filament assembly, and ML7, an inhibitor of myosin
light chain kinase, also prevent LPA stimulation of epithelial
migration. The authors suggested that Rho mediates corneal epithelial
migration in response to external stimuli by regulating the organization
of the actin cytoskeleton.
Rao et al. (2001) investigated the role of Rho kinase in the modulation
of aqueous humor outflow facility. The treatment of human trabecular
meshwork and canal of Schlemm cells with a Rho kinase-specific inhibitor
led to significant but reversible changes in cell shape and decreased
actin stress fibers, focal adhesions, and protein phosphotyrosine
staining. Based on the Rho kinase inhibitor-induced changes in myosin
light chain (see 160780) phosphorylation and actomyosin organization,
the authors suggested that cellular relaxation and loss of
cell-substratum adhesions in the human trabecular meshwork and canal of
Schlemm cells could result in either increased paracellular fluid flow
across the canal of Schlemm or altered flow pathway through the
juxtacanalicular tissue, thereby lowering resistance to outflow. They
suggested Rho kinase as a potential target for the development of drugs
to modulate intraocular pressure in glaucoma patients.
Zhou et al. (2003) found that Rho and its effector Rock1 preferentially
regulated the amount of A-beta(42), a highly amyloidogenic, 42-residue
amyloid beta (104760) peptide, produced in vitro and that only those
NSAIDs (nonsteroidal antiinflammatory drugs) effective as Rho inhibitors
lowered A-beta(42). Administration of a selective Rock inhibitor also
preferentially lowered brain levels of A-beta(42) in a transgenic mouse
model of Alzheimer disease (104300). Thus, Zhou et al. (2003) concluded
that the Rho-Rock pathway may regulate amyloid precursor protein
processing, and a subset of NSAIDs can reduce A-beta(42) through
inhibition of Rho activity.
RhoA signaling plays a critical role in many cellular processes,
including cell migration. Valderrama et al. (2006) showed that the
vaccinia F11L protein interacts directly with RhoA, inhibiting its
signaling by blocking the interaction with its downstream effectors ROCK
and mammalian Dia (300108). RNA interference-mediated depletion of F11L
during infection resulted in the absence of vaccinia-induced cell
motility and inhibition of viral morphogenesis. Disruption of the RhoA
binding site in F11L, which resembles that of ROCK, led to an identical
phenotype. Thus, Valderrama et al. (2006) concluded that inhibition of
RhoA signaling is required for both vaccinia morphogenesis and
virus-induced cell motility.
In 3-dimensional matrices, cancer cells move with a rounded, amoeboid
morphology that is controlled by ROCK1-dependent contraction of
actomyosin. Using human cancer cell lines, Pinner and Sahai (2008)
showed that PDK1 (PDPK1; 605213) was required for phosphorylation of
myosin light chain and cell motility, both on deformable gels and in
vivo. Depletion of PDK1 via RNA interference altered the localization of
ROCK1 and reduced its ability to drive cortical actomyosin contraction.
This form of ROCK1 regulation did not require PDK1 kinase activity.
Instead, PDK1 competed directly with RHOE (RND3; 602924) for binding to
ROCK1 and opposed inhibition of ROCK1 by RHOE.
Vemula et al. (2010) found that Rock1 -/- mouse macrophages and
neutrophils exhibited increased migration in vitro. Rock1 -/- bone
marrow-derived macrophages (BMMs) showed increased adhesion on a
fibronectin (see 135600) fragment. Flow cytometric analysis revealed
that Rock1 -/- BMMs had elevated F-actin compared with controls. Rock1
deficiency was associated with reduced receptor-mediated Pten (601728)
activation via serine and threonine phosphorylation, accumulation of
phosphatidylinositol 3-phosphate, and elevated downstream Pten targets.
Vemula et al. (2010) concluded that ROCK1 is a physiologic regulator of
PTEN that represses excessive recruitment of macrophages and neutrophils
during acute inflammation.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the ROCK1
gene to chromosome 18 (TMAP RH65143).
ANIMAL MODEL
Bivalacqua et al. (2004) studied the contribution of RhoA/Rho kinase
signaling to erectile dysfunction in streptozotocin (STZ) diabetic rats.
Rho kinase and eNOS (163729) colocalized in the endothelium of corpus
cavernosum, and RhoA and Rho kinase abundance and Mypt1 (602021)
phosphorylation were elevated in STZ diabetic rat penis. In addition,
eNOS protein expression, cavernosal constitutive NOS activity, and cGMP
levels were reduced in STZ diabetic rat penis. Bivalacqua et al. (2004)
introduced a dominant-negative RhoA mutant and found that erectile
responses in the STZ diabetic rats improved to values similar to
controls.
*FIELD* RF
1. Anderson, S. C.; SundarRaj, N.: Regulation of a Rho-associated
kinase expression during the corneal epithelial cell cycle. Invest.
Ophthal. Vis. Sci. 42: 933-940, 2001.
2. Bivalacqua, T. J.; Champion, H. C.; Usta, M. F.; Cellek, S.; Chitaley,
K.; Webb, R. C.; Lewis, R. L.; Mills, T. M.; Hellstrom, W. J. G.;
Kadowitz, P. J.: RhoA/Rho-kinase suppresses endothelial nitric oxide
synthase in the penis: a mechanism for diabetes-associated erectile
dysfunction. Proc. Nat. Acad. Sci. 101: 9121-9126, 2004.
3. Fujisawa, K.; Fujita, A.; Ishizaki, T.; Saito, Y.; Narumiya, S.
: Identification of the Rho-binding domain of p160-ROCK, a Rho-associated
coiled-coil containing protein kinase. J. Biol. Chem. 271: 23022-23028,
1996.
4. Ishizaki, T.; Mackawa, M.; Fujisawa, K.; Okawa, K.; Iwamatsu, A.;
Fujita, A.; Watanabe, N.; Saito, Y.; Kakisuka, A.; Morii, N.; Narumiya,
S.: The small GTP-binding protein Rho binds to and activates a 160
kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase. EMBO
J. 15: 1885-1893, 1996.
5. Maekawa, M.; Ishizaki, T.; Boku, S.; Watanabe, N.; Fujita, A.;
Iwamatsu, A.; Obinata, T.; Ohashi, K.; Mizuno, K.; Narumiya, S.:
Signaling from Rho to the actin cytoskeleton through protein kinases
ROCK and LIM-kinase. Science 285: 895-898, 1999.
6. Nakamura, M.; Nagano, T.; Chikama, T.; Nishida, T.: Role of the
small GTP-binding protein Rho in epithelial cell migration in the
rabbit cornea. Invest. Ophthal. Vis. Sci. 42: 941-947, 2001.
7. Pinner, S.; Sahai, E.: PDK1 regulates cancer cell motility by
antagonising inhibition of ROCK1 by RhoE. Nature Cell Biol. 10:
127-137, 2008. Note: Erratum: Nature Cell Biol. 10: 370 only, 2008.
8. Rao, P. V.; Deng, P.-F.; Kumar, J.; Epstein, D. L.: Modulation
of aqueous humor outflow facility by the Rho kinase-specific inhibitor
Y-27632. Invest. Ophthal. Vis. Sci. 42: 1029-1037, 2001. Note: Erratum:
Invest. Ophthal. Vis. Sci. 42: 1690 only, 2001.
9. Valderrama, F.; Cordeiro, J. V.; Schleich, S.; Frischknecht, F.;
Way, M.: Vaccinia virus-induced cell motility requires F11L-mediated
inhibition of RhoA signaling. Science 311: 377-381, 2006.
10. Vemula, S.; Shi, J.; Hanneman, P.; Wei, L.; Kapur, R.: ROCK1
functions as a suppressor of inflammatory cell migration by regulating
PTEN phosphorylation and stability. Blood 115: 1785-1796, 2010.
11. Zhou, Y.; Su, Y.; Li, B.; Liu, F.; Ryder, J. W.; Wu, X.; Gonzalez-DeWhitt,
P. A.; Gelfanova, V.; Hale, J. E.; May, P. C.; Paul, S. M.; Ni, B.
: Nonsteroidal anti-inflammatory drugs can lower amyloidogenic A-beta(42)
by inhibiting Rho. Science 302: 1215-1217, 2003.
*FIELD* CN
Patricia A. Hartz - updated: 6/1/2011
Patricia A. Hartz - updated: 10/23/2008
Ada Hamosh - updated: 4/18/2006
Patricia A. Hartz - updated: 10/27/2004
Ada Hamosh - updated: 12/3/2003
Patricia A. Hartz - updated: 10/27/2003
Jane Kelly - updated: 6/19/2001
Ada Hamosh - updated: 8/5/1999
*FIELD* CD
Lori M. Kelman: 3/11/1997
*FIELD* ED
terry: 03/14/2013
terry: 8/8/2012
mgross: 6/2/2011
terry: 6/1/2011
joanna: 1/28/2009
terry: 12/12/2008
mgross: 10/23/2008
alopez: 4/21/2006
terry: 4/18/2006
mgross: 10/27/2004
alopez: 12/8/2003
terry: 12/3/2003
cwells: 11/7/2003
cwells: 10/31/2003
terry: 10/27/2003
mcapotos: 6/20/2001
mcapotos: 6/19/2001
alopez: 8/5/1999
psherman: 7/22/1999
jenny: 3/20/1997
jenny: 3/17/1997
jenny: 3/11/1997
*RECORD*
*FIELD* NO
601702
*FIELD* TI
*601702 RHO-ASSOCIATED COILED-COIL-CONTAINING PROTEIN KINASE 1; ROCK1
;;p160-ROCK;;
read moreRHO KINASE
*FIELD* TX
CLONING
The small GTPase Rho (165390) regulates formation of focal adhesions and
stress fibers of fibroblasts, as well as adhesion and aggregation of
platelets and lymphocytes by shuttling between the inactive GDP-bound
form and the active GTP-bound form. Rho is also essential in cytokinesis
and plays a role in transcriptional activation by serum response factor
(600589). Ishizaki et al. (1996) identified the protein serine/threonine
kinase ROCK1, which they called p160-ROCK, that is activated when bound
to the GTP-bound form of Rho. Fujisawa et al. (1996) localized the
Rho-binding domain of ROCK1 to a region between residues 934-1015.
GENE FUNCTION
Maekawa et al. (1999) demonstrated that ROCK1, a downstream effector of
Rho, phosphorylates and activates LIM kinase (see 601329) which, in
turn, phosphorylates cofilin (601442), inhibiting its
actin-depolymerizing activity. They diagrammed proposed signaling
pathways for Rho-induced remodeling of the actin cytoskeleton in their
Figure 3C.
Anderson and SundarRaj (2001) noted that increased expression of ROCK1
is associated with limbal to corneal epithelial transition on the ocular
surface. In a study of the expression of ROCK1 during the cell cycle of
the corneal epithelium, they found that levels of ROCK1 were
significantly lower in the G1 phase than in the S and G0 phases.
Downregulation of ROCK1 during the G1 phase is due in part to the
decreased levels of its mRNA. The authors concluded that ROCK1 may have
a role in the progression of the cell cycle in the corneal epithelial
cells as they migrate centripetally from the limbus across the corneal
surface.
Nakamura et al. (2001) studied the role of Rho in the migration of
corneal epithelial cells in rabbit. They detected both ROCK1 and ROCK2
(604002) in the corneal epithelium at protein and mRNA levels. They
found that exoenzyme C3, a Rho inhibitor, inhibits corneal epithelial
migration in a dose-dependent manner and prevents the stimulatory effect
of the Rho activator lysophosphatidic acid (LPA). Both cytochalasin B,
an inhibitor of actin filament assembly, and ML7, an inhibitor of myosin
light chain kinase, also prevent LPA stimulation of epithelial
migration. The authors suggested that Rho mediates corneal epithelial
migration in response to external stimuli by regulating the organization
of the actin cytoskeleton.
Rao et al. (2001) investigated the role of Rho kinase in the modulation
of aqueous humor outflow facility. The treatment of human trabecular
meshwork and canal of Schlemm cells with a Rho kinase-specific inhibitor
led to significant but reversible changes in cell shape and decreased
actin stress fibers, focal adhesions, and protein phosphotyrosine
staining. Based on the Rho kinase inhibitor-induced changes in myosin
light chain (see 160780) phosphorylation and actomyosin organization,
the authors suggested that cellular relaxation and loss of
cell-substratum adhesions in the human trabecular meshwork and canal of
Schlemm cells could result in either increased paracellular fluid flow
across the canal of Schlemm or altered flow pathway through the
juxtacanalicular tissue, thereby lowering resistance to outflow. They
suggested Rho kinase as a potential target for the development of drugs
to modulate intraocular pressure in glaucoma patients.
Zhou et al. (2003) found that Rho and its effector Rock1 preferentially
regulated the amount of A-beta(42), a highly amyloidogenic, 42-residue
amyloid beta (104760) peptide, produced in vitro and that only those
NSAIDs (nonsteroidal antiinflammatory drugs) effective as Rho inhibitors
lowered A-beta(42). Administration of a selective Rock inhibitor also
preferentially lowered brain levels of A-beta(42) in a transgenic mouse
model of Alzheimer disease (104300). Thus, Zhou et al. (2003) concluded
that the Rho-Rock pathway may regulate amyloid precursor protein
processing, and a subset of NSAIDs can reduce A-beta(42) through
inhibition of Rho activity.
RhoA signaling plays a critical role in many cellular processes,
including cell migration. Valderrama et al. (2006) showed that the
vaccinia F11L protein interacts directly with RhoA, inhibiting its
signaling by blocking the interaction with its downstream effectors ROCK
and mammalian Dia (300108). RNA interference-mediated depletion of F11L
during infection resulted in the absence of vaccinia-induced cell
motility and inhibition of viral morphogenesis. Disruption of the RhoA
binding site in F11L, which resembles that of ROCK, led to an identical
phenotype. Thus, Valderrama et al. (2006) concluded that inhibition of
RhoA signaling is required for both vaccinia morphogenesis and
virus-induced cell motility.
In 3-dimensional matrices, cancer cells move with a rounded, amoeboid
morphology that is controlled by ROCK1-dependent contraction of
actomyosin. Using human cancer cell lines, Pinner and Sahai (2008)
showed that PDK1 (PDPK1; 605213) was required for phosphorylation of
myosin light chain and cell motility, both on deformable gels and in
vivo. Depletion of PDK1 via RNA interference altered the localization of
ROCK1 and reduced its ability to drive cortical actomyosin contraction.
This form of ROCK1 regulation did not require PDK1 kinase activity.
Instead, PDK1 competed directly with RHOE (RND3; 602924) for binding to
ROCK1 and opposed inhibition of ROCK1 by RHOE.
Vemula et al. (2010) found that Rock1 -/- mouse macrophages and
neutrophils exhibited increased migration in vitro. Rock1 -/- bone
marrow-derived macrophages (BMMs) showed increased adhesion on a
fibronectin (see 135600) fragment. Flow cytometric analysis revealed
that Rock1 -/- BMMs had elevated F-actin compared with controls. Rock1
deficiency was associated with reduced receptor-mediated Pten (601728)
activation via serine and threonine phosphorylation, accumulation of
phosphatidylinositol 3-phosphate, and elevated downstream Pten targets.
Vemula et al. (2010) concluded that ROCK1 is a physiologic regulator of
PTEN that represses excessive recruitment of macrophages and neutrophils
during acute inflammation.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the ROCK1
gene to chromosome 18 (TMAP RH65143).
ANIMAL MODEL
Bivalacqua et al. (2004) studied the contribution of RhoA/Rho kinase
signaling to erectile dysfunction in streptozotocin (STZ) diabetic rats.
Rho kinase and eNOS (163729) colocalized in the endothelium of corpus
cavernosum, and RhoA and Rho kinase abundance and Mypt1 (602021)
phosphorylation were elevated in STZ diabetic rat penis. In addition,
eNOS protein expression, cavernosal constitutive NOS activity, and cGMP
levels were reduced in STZ diabetic rat penis. Bivalacqua et al. (2004)
introduced a dominant-negative RhoA mutant and found that erectile
responses in the STZ diabetic rats improved to values similar to
controls.
*FIELD* RF
1. Anderson, S. C.; SundarRaj, N.: Regulation of a Rho-associated
kinase expression during the corneal epithelial cell cycle. Invest.
Ophthal. Vis. Sci. 42: 933-940, 2001.
2. Bivalacqua, T. J.; Champion, H. C.; Usta, M. F.; Cellek, S.; Chitaley,
K.; Webb, R. C.; Lewis, R. L.; Mills, T. M.; Hellstrom, W. J. G.;
Kadowitz, P. J.: RhoA/Rho-kinase suppresses endothelial nitric oxide
synthase in the penis: a mechanism for diabetes-associated erectile
dysfunction. Proc. Nat. Acad. Sci. 101: 9121-9126, 2004.
3. Fujisawa, K.; Fujita, A.; Ishizaki, T.; Saito, Y.; Narumiya, S.
: Identification of the Rho-binding domain of p160-ROCK, a Rho-associated
coiled-coil containing protein kinase. J. Biol. Chem. 271: 23022-23028,
1996.
4. Ishizaki, T.; Mackawa, M.; Fujisawa, K.; Okawa, K.; Iwamatsu, A.;
Fujita, A.; Watanabe, N.; Saito, Y.; Kakisuka, A.; Morii, N.; Narumiya,
S.: The small GTP-binding protein Rho binds to and activates a 160
kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase. EMBO
J. 15: 1885-1893, 1996.
5. Maekawa, M.; Ishizaki, T.; Boku, S.; Watanabe, N.; Fujita, A.;
Iwamatsu, A.; Obinata, T.; Ohashi, K.; Mizuno, K.; Narumiya, S.:
Signaling from Rho to the actin cytoskeleton through protein kinases
ROCK and LIM-kinase. Science 285: 895-898, 1999.
6. Nakamura, M.; Nagano, T.; Chikama, T.; Nishida, T.: Role of the
small GTP-binding protein Rho in epithelial cell migration in the
rabbit cornea. Invest. Ophthal. Vis. Sci. 42: 941-947, 2001.
7. Pinner, S.; Sahai, E.: PDK1 regulates cancer cell motility by
antagonising inhibition of ROCK1 by RhoE. Nature Cell Biol. 10:
127-137, 2008. Note: Erratum: Nature Cell Biol. 10: 370 only, 2008.
8. Rao, P. V.; Deng, P.-F.; Kumar, J.; Epstein, D. L.: Modulation
of aqueous humor outflow facility by the Rho kinase-specific inhibitor
Y-27632. Invest. Ophthal. Vis. Sci. 42: 1029-1037, 2001. Note: Erratum:
Invest. Ophthal. Vis. Sci. 42: 1690 only, 2001.
9. Valderrama, F.; Cordeiro, J. V.; Schleich, S.; Frischknecht, F.;
Way, M.: Vaccinia virus-induced cell motility requires F11L-mediated
inhibition of RhoA signaling. Science 311: 377-381, 2006.
10. Vemula, S.; Shi, J.; Hanneman, P.; Wei, L.; Kapur, R.: ROCK1
functions as a suppressor of inflammatory cell migration by regulating
PTEN phosphorylation and stability. Blood 115: 1785-1796, 2010.
11. Zhou, Y.; Su, Y.; Li, B.; Liu, F.; Ryder, J. W.; Wu, X.; Gonzalez-DeWhitt,
P. A.; Gelfanova, V.; Hale, J. E.; May, P. C.; Paul, S. M.; Ni, B.
: Nonsteroidal anti-inflammatory drugs can lower amyloidogenic A-beta(42)
by inhibiting Rho. Science 302: 1215-1217, 2003.
*FIELD* CN
Patricia A. Hartz - updated: 6/1/2011
Patricia A. Hartz - updated: 10/23/2008
Ada Hamosh - updated: 4/18/2006
Patricia A. Hartz - updated: 10/27/2004
Ada Hamosh - updated: 12/3/2003
Patricia A. Hartz - updated: 10/27/2003
Jane Kelly - updated: 6/19/2001
Ada Hamosh - updated: 8/5/1999
*FIELD* CD
Lori M. Kelman: 3/11/1997
*FIELD* ED
terry: 03/14/2013
terry: 8/8/2012
mgross: 6/2/2011
terry: 6/1/2011
joanna: 1/28/2009
terry: 12/12/2008
mgross: 10/23/2008
alopez: 4/21/2006
terry: 4/18/2006
mgross: 10/27/2004
alopez: 12/8/2003
terry: 12/3/2003
cwells: 11/7/2003
cwells: 10/31/2003
terry: 10/27/2003
mcapotos: 6/20/2001
mcapotos: 6/19/2001
alopez: 8/5/1999
psherman: 7/22/1999
jenny: 3/20/1997
jenny: 3/17/1997
jenny: 3/11/1997