Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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Rho associated coiled-coil containing protein kinase 2(ROCK2) Rho associated coiled-coil containing protein kinase 2(ROCK2) Related Genes Homo sapiens
GENERIF_SUMMARY kinetic mechanisms, ROCK-II-induced membrane blebbing and chromatin condensation require actin cytoskeleton. "ROCK-II", characterization and purification of human ROCK-II, diphosphorylated MRLC and Rho-kinase accumulated and colocalized at the contractile ring and the midbody in dividing cells, ROKalpha is regulated by CRMP-1 and CRMP2, results indicate that remnant-like particles from sudden cardiac death patients upregulate Rho-kinase in coronary vascular smooth muscle cells and markedly enhance coronary vasospastic activity, Data show that granzyme B directly cleaves ROCK II, and that this causes constitutive kinase activity and bleb formation., The crystal structure of an active Rho-kinase fragment containing the kinase domain revealed a head-to-head homodimer through the N-terminal extension forming a helix bundle that structurally integrates the C-terminal extension., Common variation in ROCK2 exerts systemic resistance-mediated changes in blood pressure and is novel mechanism for human circulatory control and suggests new possibilities for diagnosis and treatment of subjects at risk of hypertension., study investigated the role of RhoA and Rho-kinase in endothelial eNOS protein expression under hypoxic conditions, These results indicate that 2ME-induced barrier disruption is governed by microtubule depolymerization and p38- and ROCK-dependent mechanisms., Dual regulatory role for Rho kinase in fibroblast regulation in which lipid-induced Rho kinase activation suppresses fibroblast morphogenesis while TGF-beta1-induced Rho kinase activation culminates in transformation into myofibroblasts., findings report that the Notch1 gene is a p53 target in human keratinocytes with a role in tumor suppression of this cell type through negative regulation of the ROCK1/2 and MRCKalpha kinases, Plk1 and RhoA function to enhance Rock2 kinase activity in vitro and within cells, and implicate Plk1 as a regulator of multiple pathways that synergistically converge to regulate actomyosin ring contraction during cleavage furrow ingression., These findings demonstrate a central role of the GEF-H1/Rho/ROCK-II signaling pathway in the disassembly of apical junctional complex in epithelial cells., Inhibition of ROCK activity in human-derived cells enhanced either bacterial adhesion or adhesion and entry in an InlF-independent manner, further suggesting a host species or cell type-specific role for InlF., Rock1 and 2 are activated in response to wounding. ROCK activities enhance cell proliferation and epithelial differentiation, but negatively modulate cell migration and adhesion and therefore play a role in regulating corneal epithelial wound healing., Rock potently stimulates the differentiation of resting fibroblasts into myofibroblasts and the production of extracellular matrix in scleroderma fibroblasts., ROCKI and possibly ROCKII are key factors in regulation of motility/invasion of breast cancer cells, a feedback loop between Rho/ROCK, Src, and phosphorylated Cav1 in tumor cell protrusions, identifying a novel function for Cav1 in tumor metastasis that may contribute to the poor prognosis of some Cav1-expressing tumors., a major haplotype block at the ROCK2 locus is recessively associated with a lower risk of hypertension, ROCK2 activity and dimerization were dependent upon the interaction between Thr(405) of the hydrophobic motif and Asp(39) of the N-terminal extension. The reciprocal exchange of these residues was permissive for kinase activity, but not for dimerization., ROCK1 and ROCK2 regulated myosin light chain phosphatase. ROCK isoforms had distinct and opposing effects on vascular smooth muscle cell (VSMC) morphology and ROCK2, but not ROCK1, had a predominant role in VSMC contractility., Inhibition of Rho-dependent kinases ROCK I/II activates VEGF-driven retinal neovascularization and sprouting angiogenesis., overexpressed in hepatocellular carcinoma and played a significant role in regulating cytoskeletal events and contributed to the invasion of hepatocellular carcinoma, Stimulation of PKC disrupts epithelial apical junctions via ROCK-II dependent stimulation of actomyosin contractility., Data conclude that common genetic variation in ROCK2 is unlikely to make a major contribution to the risk of pre-eclampsia, but cannot exclude the possibility of having missed non-coding functional variants or rare coding variants., Provide evidence for Rho-kinase activation in patients with pulmonary arterial hypertension., These data suggest that ROCK1 and ROCK2 play distinct roles in regulating keratinocyte adhesion and terminal differentiation., Pharmacologic inhibition of Rho kinase 2 signaling blocked LPA-induced p65 phosphorylation and suppressed ICAM-1 and VCAM-1 expression., A functional proteomics approach enabled the authors to identify novel LOX-1 interactors that potentially contribute to the cellular and signaling functions of LOX-1., results suggest that miR-138 plays an important role in TSCC cell migration and invasion by concurrently targeting RhoC and ROCK2, and miR-138 may serve as a novel therapeutic target for TSCC patients at risk of metastatic disease, Results suggest that VEGF-C promoted cervical cancer metastasis by upregulation and activation of moesin protein through RhoA/ROCK-2 pathway., upregulated rho-associated protein kinase 2, p-cofilin and intracellular adhesion molecule-1, and downregulated E-cadherin were found in esophageal squamous cell cancer cells, Thr431Asn polymorphism of the ROCK2 gene could be a risk factor for the metastases of the breast cancer, and may help in predicting the prognosis., Expression of miR-139 is reduced in human metastatic hepatocellular carcinoma samples and correlates with prognosis. The microRNA miR-139 interacts with ROCK2 and reduces its expression in hepatocellular carcinoma., The results of this study suggested that there were no evidence for an association of ROCK2 gene Thr431Asn and Arg83Lys polymorphisms with diabetes or diabetic retinopathy in the Turkish population., results suggested that a complex consisting of BRCA2, NPM, and ROCK2 maintains the numerical integrity of centrosomes and accurate cell division and that dysfunction of this regulation might be involved in the tumorigenesis of breast cancer, LR11 is phosphorylated in vivo and indicate that ROCK2 phosphorylation of LR11 may enhance LR11 mediated processing of APP and amyloid production., Ras/Raf/MAPK and RhoA/ROCKII signalling pathways are abnormally activated in eutopic endometrial stromal cells of patients with endometriosis, A novel mechanism for controlling ROCKII localization at the membrane, in which the ROCKII C-terminus acts as a coincidence detector for spatial regulatory signals., The up-regulated expression of ROCK2 is correlated with patient age and differentiation grade of esophageal squamous cell carcinoma., ROCK1 has a role in regulating myometrial contractility., Results demonstrate differential effects of Snail and Slug in pancreatic cancer and identify the interplay between Rho signaling and beta1-integrin that regulates the scattering and migration of Snail- and Slug-expressing pancreatic cancer cells., It was concluded that RhoA/ROCK is active in the internal anal sphincter (IAS), and is the critical determinant of the basal tone in intact human IAS and that they are potential therapeutic targets for a number of rectoanal motility disorders., We found that the extent of Ser1366 phosphorylation of endogenous ROCKII is correlated with that of myosin light chain phosphorylation in cells in response to RhoA stimulation, showing that Ser1366 phosphorylation reflects its kinase activity, ROCK1 and ROCK2 have distinct and separate roles in adhesion complex assembly and turnover in human epidermal keratinocytes., We conclude that ROCK proteins are necessary for acquisition of elongated and geometric cell shape, two key events for epithelial differentiation., A new role for Rock2 in modulation of Cdc25A ubiquitination has been revealed, indicating a novel mechanism of Cdc25A regulation and a potential function for Rock2 in the development of hepatocellular carcinoma., our overall results reveal a model whereby CD1d-mediated Ag presentation is negatively regulated by ROCK1 and ROCK2 via its effects on the actin cytoskeleton., Angiotensin II induces the contraction of airway smooth muscle cells; this effect can be reversed by Ang-(1-7), partially through the downregulation of of the RhoA/ROCK2 signaling pathway., The results strongly suggest that ROCK2 gene polymorphisms may modify individual susceptibility to Behcet's disease in the Turkish population., suppression of ROCK1 or ROCK2 expression alone was sufficient to impair anchorage-independent growth, supporting their nonoverlapping roles in oncogenesis, the two isoforms of Rho-kinase distribute differentially to accomplish their specific functions, These results suggest that ROCK2 might mediate bFGF-induced proliferation of SH-SY5Y cells through GSK-3beta and beta-catenin pathway, The relationship between the ROCK2 polymorphisms and cardiovascular disease risk cannot be entirely discounted and warrants further evaluation in a large population., Our data showed that the ROCK1 and ROCK2 genes might be a risk factor for colorectal cancer development, Sulfide induces both ROCK-1 and ROCK-2 cleavage and causes ROCKdependent cell blebbing during apoptosis., Results suggest miR-126 function as a potential tumor suppressor in colon cancer progression and miR-126/RhoA/ROCK may be a novel candidate for developing rational therapeutic strategies., we have shown that forced expression of wild-type CD99 in osteosarcoma cells induces downregulation of genes such as ROCK2, Immunohistochemical and western blot analyses showed no change in ROCK1 and ROCK2 protein expressions in Barrett's esophagus, CRMP-2-dependent regulation of ROCK II activity is mediated through interaction of the CRMP-2L N terminus with the ROCK II catalytic domain as well as by GSK3-dependent phosphorylation of CRMP-2., Testosterone induces actin cytoskeleton remodeling by regulating ROCK-2/moesin expression and activation., ROCK2 in vascular smooth cells contributes to the pathogenesis of hypoxia-induced pulmonary arterial hypertension., Active ROCKI is phosphorylated at Ser1333 site. Antibodies that recognize phospho-Ser1333 of ROCKI and phospho-S1366 residues of ROCKII offer a means to discriminate their individual active status in cells and tissues., Selective knockdown of ROCK2 exerted antidromic effects on glioma migration., Loss of TSC2 expression can alter microtubule organization and dynamics, which, in turn, deregulate cell division and potentially impair neuronal differentiation via ROCK2 signaling., ROCK2 gene Thr431Asn polymorphism is not a risk factor for migraine in the Turkish population., Study reports a unique, PGE2-induced, functional inhibitory phosphoS1379 site on ROCK2 that mutational analysis con fi rms is critical to the activity of the enzyme in terms of myosin light chain II and paxillin phosphorylation, hence controlling the formation of stress fi bres and focal adhesions in fibroblast-myo fi broblast transitions., morgana causes PTEN destabilization, by inhibiting ROCK activity, This is the first study to examine the involvement of ROCK1 and ROCK2 gene variations in the risk of primary open-angle glaucoma development., These results suggest that there is no association of the ROCK2 gene Thr431Asn polymorphism with the development of cardiac septal defects in pediatric patients., ROCK-II was activated in various lung cells of patients with idiopathic pulmonary fibrosis along with oxidative stress detected by 8-isoPGF2alpha elevation., protein kinase (ROCK)-focal adhesion kinase (p-FAK cascade plays an important role in the effect of caffeine in glioma cells., upregulation of MMP2 rescued the decreased migration and invasion induced by the knockdown of Rock2, whereas the knockdown of MMP2 decreased Rock2-enhanced hepatocellular carcinoma migration and invasion, miR-200b and miR-200c are suppressed in AGE-induced endothelial cell injury, resulting in unregulated RhoA/ROCK2 signaling., Two functional single nucleotide polymorphisms of ROCK2 increase susceptibility of arterial stiffness in the Chinese population., ROCK2 is required for CXCL8 responses by TNF-alpha stimulated IEC by affecting intracellular signaling through MKK4 adn JNK., Depletion of the kinases ROCK1 and ROCK2, two known RhoC downstream effectors, similarly decreases cancer interaction with ECs, Our data indicate that expression of ROCK1 and ROCK2 are closely associated with tumor growth and lymph node metastasis of laryngeal squamous cell carcinoma, Data indicate that dysfunction of the Rho-associated kinase 2 (Rock2)-p-GSK3beta/beta-catenin-CCAAT/enhancer-binding protein delta (CEBPD) regulatory circuitry may contribute to the tumorigenic characteristic of hepatocellular carcinoma (HCC)., our data suggest that inhibition of ROCK (Rho-kinases ROCK 1 and ROCK 2)reduces the ability of melanoma cells to efficiently colonize the lungs, ROCK2 is pivotal to baseline junctional tension as a novel mechanism by which Rho kinase primes the endothelium for hyperpermeability responses., knockdown of TMEM45A also inhibited cell adhesion as well as cell invasion. More importantly, suppression of TMEM45A notably downregulated the expression of TGF-b1, TGF-b2, RhoA and ROCK2., Results demonstrated that the miR-200b/200c/429 subfamily inhibited HCC cell migration through modulating Rho/ROCK mediated cell cytoskeletal reorganization and cell-substratum adhesion., miR-144 suppresses OS progression by directly downregulating ROCK1 and ROCK2 expression., These results indicate that bleb formation is dependent on Rho activity (ROCK1 and ROCK 2)in ouabain-induced cell death in HUVECs, 17beta-estradiol induces proliferation of uterine smooth muscle cells in endometriosis through hyperactivation of the estrogen receptor-RhoA/ROCK signaling pathway., miR-448 may contribute to the progression of Hepatocellular Carcinoma via regulating ROCK2 expression., Esophageal squamous cell carcinoma showed a positive expression of Rock2, which was significantly association with ethnic background., We speculate that the drop of the ROCK-to-MLCK ratio may occur as an attempt to compensate for the increased Rho kinase activity., ROCK activity in MS serum was elevated compared with serum from healthy controls, beta-catenin/TCF4 pathway contributed to the effects of Rock2 in CRC cells, and Rock2 stabilized beta-catenin by preventing its ubiquitination and degradation, no differences in renal interstitial fibrosis or UUOinduced ROCK activity were identified between the ROCK2 heterozygote knockout and WT mice, indicating that the genetic partial disruption of ROCK2 is insufficient for protecting against renal fibrosis., ROCK2 forms a dimer, 120 nm in length, with a long coiled-coil tether linking the kinase and membrane-binding domains., Study shows that nuclear ROCKII activation signal might contribute to the tumor metastasis in breast cancer., This study report that protein levels of the Rho-associated protein kinases (ROCK2) was increased in Progressive Supranuclear Palsy and Corticobasal Degeneration brains., Rho Kinase ROCK2 Mediates Acid-Induced NADPH Oxidase NOX5-S Expression in Human Esophageal Adenocarcinoma Cells,
SP_COMMENT catalytic activity:ATP + a protein = ADP + a phosphoprotein., enzyme regulation:Activated by RHOA binding., function:Protein kinase that phosphorylates a large number of important signaling proteins, and thereby regulates the assembly of the actin cytoskeleton. Promotes formation of stress fibers and of focal adhesion complexes. Plays a role in smooth muscle contraction., miscellaneous:Inhibited by Y-27632., PTM:Phosphorylated upon DNA damage, probably by ATM or ATR., similarity:Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family., similarity:Contains 1 AGC-kinase C-terminal domain., similarity:Contains 1 PH domain., similarity:Contains 1 phorbol-ester/DAG-type zinc finger., similarity:Contains 1 protein kinase domain., similarity:Contains 1 REM (Hr1) repeat., subcellular location:Cytoplasmic, and associated with actin microfilaments and the plasma membrane., subunit:Homodimer. Binds RHOA that has been activated by GTP binding. Binds IRS1, RHOB and RHOC.,