Genomes and Genes
Gene Symbol: ROCK1
Description: Rho associated coiled-coil containing protein kinase 1
Alias: P160ROCK, ROCK-I, rho-associated protein kinase 1, p160 ROCK-1, renal carcinoma antigen NY-REN-35
- Lochhead P, Wickman G, Mezna M, Olson M. Activating ROCK1 somatic mutations in human cancer. Oncogene. 2010;29:2591-8 pubmed publisher..b>ROCK1 is an essential effector kinase downstream of Rho GTPases, an important pathway involved in cell migration...
- Lane J, Martin T, Watkins G, Mansel R, Jiang W. The expression and prognostic value of ROCK I and ROCK II and their role in human breast cancer. Int J Oncol. 2008;33:585-93 pubmed..This, together with significant correlation between ROCKI and poor outcome in clinical breast cancer, indicates that it is a potential target in human breast cancer. ..
- Ongusaha P, Kim H, Boswell S, Ridley A, Der C, Dotto G, et al. RhoE is a pro-survival p53 target gene that inhibits ROCK I-mediated apoptosis in response to genotoxic stress. Curr Biol. 2006;16:2466-72 pubmed..We found that RhoE inhibits ROCK I (Rho-associated kinase I) activity during genotoxic stress and thereby suppresses apoptosis...
- Pedrini S, Carter T, Prendergast G, Petanceska S, Ehrlich M, Gandy S. Modulation of statin-activated shedding of Alzheimer APP ectodomain by ROCK. PLoS Med. 2005;2:e18 pubmed..enzymes play a role in statin-stimulated shedding has been excluded, leading us to investigate whether the Rho/ROCK1 protein phosphorylation pathway might be involved...
- Sahai E, Marshall C. ROCK and Dia have opposing effects on adherens junctions downstream of Rho. Nat Cell Biol. 2002;4:408-15 pubmed..The ability of Dia1 to regulate the actin network is crucial for the localization of adherens junction components to the cell periphery. ..
- Velasco G, Armstrong C, Morrice N, Frame S, Cohen P. Phosphorylation of the regulatory subunit of smooth muscle protein phosphatase 1M at Thr850 induces its dissociation from myosin. FEBS Lett. 2002;527:101-4 pubmed..Here, we show that the phosphorylation of Thr850 by Rho kinase dissociates PP1M from myosin, providing a second mechanism by which myosin phosphatase activity is inhibited. ..
- Liu X, Choy E, Hornicek F, Yang S, Yang C, Harmon D, et al. ROCK1 as a potential therapeutic target in osteosarcoma. J Orthop Res. 2011;29:1259-66 pubmed publisher..cell growth and proliferation have identified the Rho-associated coiled-coil containing protein kinase 1 (ROCK1) as a possible hit...
- Hopkins A, Pineda A, Winfree L, Brown G, Laukoetter M, Nusrat A. Organized migration of epithelial cells requires control of adhesion and protrusion through Rho kinase effectors. Am J Physiol Gastrointest Liver Physiol. 2007;292:G806-17 pubmed
- Wilkinson S, Paterson H, Marshall C. Cdc42-MRCK and Rho-ROCK signalling cooperate in myosin phosphorylation and cell invasion. Nat Cell Biol. 2005;7:255-61 pubmed..Our data show that a Cdc42-MRCK signal mediates myosin-dependent cell motility and highlight convergence between Rho and Cdc42 signalling. ..
- Amano M, Nakayama M, Kaibuchi K. Rho-kinase/ROCK: A key regulator of the cytoskeleton and cell polarity. Cytoskeleton (Hoboken). 2010;67:545-54 pubmed publisher..This review focuses on the structure, function, and modes of activation and action of Rho-kinase. ..
- Tu D, Li Y, Song H, Toms A, Gould C, Ficarro S, et al. Crystal structure of a coiled-coil domain from human ROCK I. PLoS ONE. 2011;6:e18080 pubmed publisher..Here we present the crystal structure of a large section of the central coiled-coil domain of human ROCK I (amino acids 535-700)...
- Ohta Y, Hartwig J, Stossel T. FilGAP, a Rho- and ROCK-regulated GAP for Rac binds filamin A to control actin remodelling. Nat Cell Biol. 2006;8:803-14 pubmed..FilGAP is, therefore, a mediator of the well-established antagonism of Rac by RhoA that suppresses leading edge protrusion and promotes cell retraction to achieve cellular polarity. ..
- Shields M, Krantz S, Bentrem D, Dangi Garimella S, Munshi H. Interplay between ?1-integrin and Rho signaling regulates differential scattering and motility of pancreatic cancer cells by snail and Slug proteins. J Biol Chem. 2012;287:6218-29 pubmed publisher..In contrast, inhibiting Rho-associated kinase ROCK1/2 increased migration and scattering of Slug-expressing cells in three-dimensional collagen and thus phenocopied ..
- Gurkar A, Chu K, Raj L, Bouley R, Lee S, Kim Y, et al. Identification of ROCK1 kinase as a critical regulator of Beclin1-mediated autophagy during metabolic stress. Nat Commun. 2013;4:2189 pubmed publisherThe Ser/Thr Rho kinase 1 (ROCK1) is known to have major roles in a wide range of cellular activities, including those involved in tumour metastasis and apoptosis...
- Pinner S, Sahai E. PDK1 regulates cancer cell motility by antagonising inhibition of ROCK1 by RhoE. Nat Cell Biol. 2008;10:127-37 pubmed publisher..Depletion of PDK1 alters the localization of ROCK1 and reduces its ability to drive cortical acto-myosin contraction...
- Shin J, Kim Y, Cho S, Lee M, Kook M, Lee J, et al. MicroRNA 135a suppresses lymph node metastasis through down-regulation of ROCK1 in early gastric cancer. PLoS ONE. 2014;9:e85205 pubmed publisher..b>ROCK1 was a target of miRNA-135a and its expression was inversely correlated to that of miRNA-135a...
- Kawano Y, Fukata Y, Oshiro N, Amano M, Nakamura T, Ito M, et al. Phosphorylation of myosin-binding subunit (MBS) of myosin phosphatase by Rho-kinase in vivo. J Cell Biol. 1999;147:1023-38 pubmed
- Lock F, Hotchin N. Distinct roles for ROCK1 and ROCK2 in the regulation of keratinocyte differentiation. PLoS ONE. 2009;4:e8190 pubmed publisher..The mammalian serine/threonine kinases (ROCK1 and ROCK2) are well-characterised downstream effectors of the small GTPase RhoA...
- Komander D, Garg R, Wan P, Ridley A, Barford D. Mechanism of multi-site phosphorylation from a ROCK-I:RhoE complex structure. EMBO J. 2008;27:3175-85 pubmed publisher..We propose that ROCK-I phosphorylation of RhoE forms part of a feedback loop to regulate RhoA signalling. ..
- Kaneko K, Satoh K, Masamune A, Satoh A, Shimosegawa T. Expression of ROCK-1 in human pancreatic cancer: its down-regulation by morpholino oligo antisense can reduce the migration of pancreatic cancer cells in vitro. Pancreas. 2002;24:251-7 pubmed..These results suggest that ROCK-1 may contribute to pancreatic cancer cell invasion and/or metastasis by facilitating cancer cell migration. ..
- Wong C, Wong C, Ko F, Chan L, Ching Y, Yam J, et al. Deleted in liver cancer 1 (DLC1) negatively regulates Rho/ROCK/MLC pathway in hepatocellular carcinoma. PLoS ONE. 2008;3:e2779 pubmed publisher..This implicates a ROCK-mediated pathway of DLC1 in suppressing metastasis of HCC cells and enriches our understanding in the molecular mechanisms involved in the progression of hepatocellular carcinoma. ..
- Arimura N, Inagaki N, Chihara K, Menager C, Nakamura N, Amano M, et al. Phosphorylation of collapsin response mediator protein-2 by Rho-kinase. Evidence for two separate signaling pathways for growth cone collapse. J Biol Chem. 2000;275:23973-80 pubmed..These results demonstrate the existence of Rho-kinase-dependent and -independent pathways for growth cone collapse and suggest that CRMP-2 phosphorylation by Rho-kinase is involved in the former pathway. ..
- Ohashi K, Nagata K, Maekawa M, Ishizaki T, Narumiya S, Mizuno K. Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop. J Biol Chem. 2000;275:3577-82 pubmed
- Kosako H, Amano M, Yanagida M, Tanabe K, Nishi Y, Kaibuchi K, et al. Phosphorylation of glial fibrillary acidic protein at the same sites by cleavage furrow kinase and Rho-associated kinase. J Biol Chem. 1997;272:10333-6 pubmed..Furthermore, the phosphorylation of GFAP by Rho-kinase results in a nearly complete inhibition of its filament formation in vitro. The possibility that Rho-kinase is a candidate for cleavage furrow kinase is discussed. ..
- Hannemann S, Madrid R, Stastna J, Kitzing T, Gasteier J, Schönichen A, et al. The Diaphanous-related Formin FHOD1 associates with ROCK1 and promotes Src-dependent plasma membrane blebbing. J Biol Chem. 2008;283:27891-903 pubmed publisher..we report that FHOD1 physically associates via the N-terminal part of its FH2 domain with the central domain of ROCK1. Although FHOD1 does not affect the kinase activity of ROCK1, the DRF is an efficient substrate for ..
- Hebert M, Potin S, Sebbagh M, Bertoglio J, Bréard J, Hamelin J. Rho-ROCK-dependent ezrin-radixin-moesin phosphorylation regulates Fas-mediated apoptosis in Jurkat cells. J Immunol. 2008;181:5963-73 pubmed..Thus, phosphorylation of E/M by ROCK is involved in the early steps of apoptotic signaling following Fas triggering and regulates apoptosis induction. ..
- Han Z, Xu G, Zhou J, Xing H, Wang S, Wu M, et al. Inhibition of motile and invasive properties of ovarian cancer cells by ASODN against Rho-associated protein kinase. Cell Commun Adhes. 2005;12:59-69 pubmedb>p160ROCK, a kinase effector of Rho GTPase mediating RhoA-induced assembly of focal adhesions and stress fibers, plays an important role in the invasive process of various tumor cells...
- Zheng B, Liang L, Wang C, Huang S, Cao X, Zha R, et al. MicroRNA-148a suppresses tumor cell invasion and metastasis by downregulating ROCK1 in gastric cancer. Clin Cancer Res. 2011;17:7574-83 pubmed publisher..In addition, overexpression of miR-148a in GC cells could reduce the mRNA and protein levels of ROCK1, whereas miR-148a silencing significantly increased ROCK1 expression...
- Basile J, Gavard J, Gutkind J. Plexin-B1 utilizes RhoA and Rho kinase to promote the integrin-dependent activation of Akt and ERK and endothelial cell motility. J Biol Chem. 2007;282:34888-95 pubmed..These findings provide evidence that Plexin-B1 promotes endothelial cell motility through RhoA and ROK by regulating the integrin-dependent signaling networks that result in the activation of PI3K and Akt. ..
- Matsui T, Maeda M, Doi Y, Yonemura S, Amano M, Kaibuchi K, et al. Rho-kinase phosphorylates COOH-terminal threonines of ezrin/radixin/moesin (ERM) proteins and regulates their head-to-tail association. J Cell Biol. 1998;140:647-57 pubmed
- Riento K, Guasch R, Garg R, Jin B, Ridley A. RhoE binds to ROCK I and inhibits downstream signaling. Mol Cell Biol. 2003;23:4219-29 pubmed..Here, we show that RhoE binds ROCK I but none of the other RhoA targets tested...
- Ongusaha P, Qi H, Raj L, Kim Y, Aaronson S, Davis R, et al. Identification of ROCK1 as an upstream activator of the JIP-3 to JNK signaling axis in response to UVB damage. Sci Signal. 2008;1:ra14 pubmed publisher..of the JNK-interacting protein 3 (JIP-3) scaffolding protein as an interacting partner of Rho-associated kinase 1 (ROCK1), as determined by tandem affinity protein purification...
- Narumiya S, Tanji M, Ishizaki T. Rho signaling, ROCK and mDia1, in transformation, metastasis and invasion. Cancer Metastasis Rev. 2009;28:65-76 pubmed publisher..Thus, Rho mediates various phenotypes of malignant transformation by Ras and Src through its effectors, ROCK and mDia. ..
- Feng J, Ito M, Ichikawa K, Isaka N, Nishikawa M, Hartshorne D, et al. Inhibitory phosphorylation site for Rho-associated kinase on smooth muscle myosin phosphatase. J Biol Chem. 1999;274:37385-90 pubmed..In summary, these results offer strong support for a physiological role of Rho-kinase in regulation of MP activity. ..
- Li Z, Dong X, Dong X, Wang Z, Liu W, Deng N, et al. Regulation of PTEN by Rho small GTPases. Nat Cell Biol. 2005;7:399-404 pubmed..Furthermore, we have identified key residues on PTEN that are required for its regulation by the small GTPase, and show that small GTPase-mediated regulation of PTEN has a significant role in the regulation of chemotaxis. ..
- Do e Z, Fukumoto Y, Takaki A, Tawara S, Ohashi J, Nakano M, et al. Evidence for Rho-kinase activation in patients with pulmonary arterial hypertension. Circ J. 2009;73:1731-9 pubmed..These results provide the first direct evidence for Rho-kinase activation in patients with PAH, suggesting the therapeutic importance of Rho-kinase in the disorder. ..
- Deng L, Li G, Li R, Liu Q, He Q, Zhang J. Rho-kinase inhibitor, fasudil, suppresses glioblastoma cell line progression in vitro and in vivo. Cancer Biol Ther. 2010;9:875-84 pubmed..The Rho/ROCK signaling pathway may prove to be a promising target in anti-tumor therapy. Fasudil may be an attractive anti-tumor drug candidate for the treatment of GBM. ..
- Ueno K, Hirata H, Shahryari V, Chen Y, Zaman M, Singh K, et al. Tumour suppressor microRNA-584 directly targets oncogene Rock-1 and decreases invasion ability in human clear cell renal cell carcinoma. Br J Cancer. 2011;104:308-15 pubmed publisher..The knockdown of ROCK-1 by siRNA inhibited cell motility. miR-584 is a new tumour suppressor miR in ccRCC and inhibits cell motility through downregulation of ROCK-1. ..
- Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, et al. Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science. 1999;285:895-8 pubmed..These results indicate that phosphorylation of LIM-kinase by ROCK and consequently increased phosphorylation of cofilin by LIM-kinase contribute to Rho-induced reorganization of the actin cytoskeleton. ..
- Jacobs M, Hayakawa K, Swenson L, Bellon S, Fleming M, Taslimi P, et al. The structure of dimeric ROCK I reveals the mechanism for ligand selectivity. J Biol Chem. 2006;281:260-8 pubmed..Hydroxyfasudil, a metabolite of fasudil, may be selective for ROCK over PKA through a reversed binding orientation. ..
- Ishizaki T, Maekawa M, Fujisawa K, Okawa K, Iwamatsu A, Fujita A, et al. The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase. EMBO J. 1996;15:1885-93 pubmed..When co-expressed with RhoA in COS cells, p160 was co-precipitated with the expressed Rho and its kinase activity was activated, indicating that p160 can associate physically and functionally with Rho both in vitro and in vivo. ..
- Oshiro N, Fukata Y, Kaibuchi K. Phosphorylation of moesin by rho-associated kinase (Rho-kinase) plays a crucial role in the formation of microvilli-like structures. J Biol Chem. 1998;273:34663-6 pubmed..These results indicate that Rho-kinase regulates moesin phosphorylation downstream of Rho in vivo and that the phosphorylation of moesin by Rho-kinase plays a crucial role in the formation of microvilli-like structures. ..
- Nakai K, Suzuki Y, Kihira H, Wada H, Fujioka M, Ito M, et al. Regulation of myosin phosphatase through phosphorylation of the myosin-binding subunit in platelet activation. Blood. 1997;90:3936-42 pubmed..These findings suggest a putative mechanism for agonist-induced regulation of myosin phosphatase activity in platelets. ..
- Dvorsky R, Blumenstein L, Vetter I, Ahmadian M. Structural insights into the interaction of ROCKI with the switch regions of RhoA. J Biol Chem. 2004;279:7098-104 pubmed..The identified ROCK-binding site of RhoA strikingly supports the assumption of a common consensus-binding site for effector recognition. ..
- Le Boeuf F, Houle F, Huot J. Regulation of vascular endothelial growth factor receptor 2-mediated phosphorylation of focal adhesion kinase by heat shock protein 90 and Src kinase activities. J Biol Chem. 2004;279:39175-85 pubmed..Our findings underscore for the first time the key role played by the VEGFR2-HSP90-RhoA-ROCK-FAK/Tyr(407) pathway in transducing the VEGF signal that leads to the assembly of focal adhesions and endothelial cell migration. ..
- Chen J, Ye L, Zhang L, Jiang W. Placenta growth factor, PLGF, influences the motility of lung cancer cells, the role of Rho associated kinase, Rock1. J Cell Biochem. 2008;105:313-20 pubmed publisher..Immunocytochemistry and Western blotting further revealed that the expression of ROCK1, Rho associated kinase, was also reduced in A549(DeltaPlGF) cells, in comparison with wild-type and control cells...
- Goto H, Kosako H, Tanabe K, Yanagida M, Sakurai M, Amano M, et al. Phosphorylation of vimentin by Rho-associated kinase at a unique amino-terminal site that is specifically phosphorylated during cytokinesis. J Biol Chem. 1998;273:11728-36 pubmed
- Giagulli C, Magiera A, Bugatti A, Caccuri F, Marsico S, Rusnati M, et al. HIV-1 matrix protein p17 binds to the IL-8 receptor CXCR1 and shows IL-8-like chemokine activity on monocytes through Rho/ROCK activation. Blood. 2012;119:2274-83 pubmed publisher..Recent studies have highlighted the role of IL-8 and CXCR1 in HIV-1 replication and AIDS pathogenesis. Our findings herein call for an exploration of the therapeutic potential of blocking the p17/IL-8/CXCR1 axis in HIV-1 infection. ..
- Fujisawa K, Fujita A, Ishizaki T, Saito Y, Narumiya S. Identification of the Rho-binding domain of p160ROCK, a Rho-associated coiled-coil containing protein kinase. J Biol Chem. 1996;271:23022-8 pubmed..Furuyashiki, T., Ishizaki, T., Watanabe, G., Watanabe, N., Fujisawa, K., Morii, N., Madaule, P., and Narumiya, S. (1996) J. Biol. Chem. 271, 13556-13560) and may define a distinct class of Rho effector motif. ..
- Sebbagh M, Renvoizé C, Hamelin J, Riche N, Bertoglio J, Breard J. Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing. Nat Cell Biol. 2001;3:346-52 pubmed..Here we identify ROCK I, an effector of the small GTPase Rho, as a new substrate for caspases...
- Patel R, Forinash K, Pireddu R, Sun Y, Sun N, Martin M, et al. RKI-1447 is a potent inhibitor of the Rho-associated ROCK kinases with anti-invasive and antitumor activities in breast cancer. Cancer Res. 2012;72:5025-34 pubmed publisherThe Rho-associated kinases ROCK1 and ROCK2 are critical for cancer cell migration and invasion, suggesting they may be useful therapeutic targets...
- Li F, Jiang Q, Shi K, Luo H, Yang Y, Xu C. RhoA modulates functional and physical interaction between ROCK1 and Erk1/2 in selenite-induced apoptosis of leukaemia cells. Cell Death Dis. 2013;4:e708 pubmed publisher..RhoA, regulating Rho-associated coiled-coil-forming kinase 1 (ROCK1), modulates multiple cell functions, including malignant transformation, metastasis and cell death...
- Kitazawa T, Eto M, Woodsome T, Khalequzzaman M. Phosphorylation of the myosin phosphatase targeting subunit and CPI-17 during Ca2+ sensitization in rabbit smooth muscle. J Physiol. 2003;546:879-89 pubmed
- Edwards D, Sanders L, Bokoch G, Gill G. Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics. Nat Cell Biol. 1999;1:253-9 pubmed..A Pak1-specific inhibitor, corresponding to the Pak1 autoinhibitory domain, blocks LIM-kinase-induced cytoskeletal changes. Activated GTPases can thus regulate actin depolymerization through Pak1 and LIM-kinase. ..
- Xu X, Song Q, Yao Y, Ruan P, Tao Z. Inhibition of RhoA/ROCK signaling pathway promotes the apoptosis of gastric cancer cells. Hepatogastroenterology. 2012;59:2523-6 pubmed..RhoA RNAi caused an obvious decrease of ROCK1 expression but an increase of caspase-3/cleaved-caspase-8...
- Leung T, Chen X, Manser E, Lim L. The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton. Mol Cell Biol. 1996;16:5313-27 pubmed
- Chang J, Xie M, Shah V, Schneider M, Entman M, Wei L, et al. Activation of Rho-associated coiled-coil protein kinase 1 (ROCK-1) by caspase-3 cleavage plays an essential role in cardiac myocyte apoptosis. Proc Natl Acad Sci U S A. 2006;103:14495-500 pubmed..These data suggest an obligatory role for ROCK-1 cleavage in promoting apoptotic signals in myocardial hypertrophy and/or failure. ..
- Zhang C, Zhang S, Zhang Z, He J, Xu Y, Liu S. ROCK has a crucial role in regulating prostate tumor growth through interaction with c-Myc. Oncogene. 2014;33:5582-91 pubmed publisher..We provided evidence demonstrating that ROCK1 directly interacted with and phosphorylated c-Myc, resulting in stabilization of the protein and activation of its ..
- Shichi D, Arimura T, Ishikawa T, Kimura A. Heart-specific small subunit of myosin light chain phosphatase activates rho-associated kinase and regulates phosphorylation of myosin phosphatase target subunit 1. J Biol Chem. 2010;285:33680-90 pubmed publisher..In addition, hHS-M(21) bound ROCK and enhanced the ROCK activity. These findings suggest that hHS-M(21) is a heart-specific effector of ROCK and plays a regulatory role in the MYPT1 phosphorylation at Thr-696 by ROCK. ..
- Wang Y, Zhao W, Fu Q. miR-335 suppresses migration and invasion by targeting ROCK1 in osteosarcoma cells. Mol Cell Biochem. 2013;384:105-11 pubmed publisher..Moreover, we also showed that ROCK1 was negatively regulated by miR-335 at the posttranscriptional level, via a specific target site within the 3'UTR ..
- Zhou X, Wei M, Wang W. MicroRNA-340 suppresses osteosarcoma tumor growth and metastasis by directly targeting ROCK1. Biochem Biophys Res Commun. 2013;437:653-8 pubmed publisher..b>ROCK1 was identified as a target of miR-340, and ectopic expression of miR-340 downregulated ROCK1 by direct binding to ..
- Wang Y, Zheng X, Riddick N, Bryden M, Baur W, Zhang X, et al. ROCK isoform regulation of myosin phosphatase and contractility in vascular smooth muscle cells. Circ Res. 2009;104:531-40 pubmed publisher..Two ROCK isoforms, ROCK1 and ROCK2, are expressed in many tissues, yet the isoform-specific roles of ROCK1 and ROCK2 in vascular smooth ..
- Lock F, Ryan K, Poulter N, Parsons M, Hotchin N. Differential regulation of adhesion complex turnover by ROCK1 and ROCK2. PLoS ONE. 2012;7:e31423 pubmed publisherb>ROCK1 and ROCK2 are serine/threonine kinases that function downstream of the small GTP-binding protein RhoA...
- Mali R, Ramdas B, Ma P, Shi J, Munugalavadla V, Sims E, et al. Rho kinase regulates the survival and transformation of cells bearing oncogenic forms of KIT, FLT3, and BCR-ABL. Cancer Cell. 2011;20:357-69 pubmed publisher..In summary we describe a pathway involving PI3K/Rho/ROCK/MLC that may contribute to myeloproliferative disease and/or acute myeloid leukemia in humans. ..
- Shao J, Welch W, DiProspero N, Diamond M. Phosphorylation of profilin by ROCK1 regulates polyglutamine aggregation. Mol Cell Biol. 2008;28:5196-208 pubmed publisher..identified profilin, a small actin-binding factor that also interacts with Htt, as being a direct target of the ROCK1 isoform...