p160<sup>ROCK</sup>, a Rho‐associated coiled‐coil forming protein kinase, works downstream of Rho and induces focal adhesions

Ishizaki, Toshimasa; Naito, Mamoru; Fujisawa, Katsuki; Maekawa, Masao; Watanabe, Naoki; Saito, Yuji; Narumiya, Shuh

doi:10.1016/s0014-5793(97)00107-5

Cited by 481 publications

(431 citation statements)

References 21 publications

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“…ROCK can increase MLC phosphorylation through direct effect on MLC or indirectly by inactivating MLC phosphatase. The increased MLC phosphorylation results in stimulation of actomyosin contractility [2,55,73]. Inactivation of MLC phosphatase by ROCK plays an important physiological role such as agonist-induced Ca 2+ sensitization in smooth muscle contraction [28,29,141].…”

Section: Substrates Of Rockmentioning

confidence: 99%

Rho kinase in the regulation of cell death and survival

Shi

Wei

2007

Arch. Immunol. Ther. Exp.

211

181

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SummaryRho kinase (ROCK) belongs to a family of serine/threonine kinases that are activated via interaction with Rho GTPases. ROCK is involved in a wide range of fundamental cellular functions such as contraction, adhesion, migration, and proliferation. Recent studies have shown that ROCK plays an important role in the regulation of apoptosis in various cell types and animal disease models. Two ROCK isoforms, ROCK1 and ROCK2, are assumed to be function redundant, based largely on kinase construct overexpression, and chemical inhibitors (Y27632 and fasudil), which inhibit both ROCK1 and ROCK2. Gene targeting and RNA interference approaches allow further dissection of distinct cellular, physiological and patho-physiological functions of the two ROCK isoforms. This review, based on recent molecular, cellular and animal studies, focuses on the current understanding of ROCK signaling in the regulation of apoptosis and highlights the new findings from recently generated ROCK-deficient mice.

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Section: Substrates Of Rockmentioning

confidence: 99%

Rho kinase in the regulation of cell death and survival

Shi

Wei

2007

Arch. Immunol. Ther. Exp.

211

181

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“…The Rho-associated kinase (p160ROCK) is known to be one of the main downstream targets of RhoA signalling, and it is involved in the reorganization of the cytoskeleton and focal adhesions [Ishizaki et al, 1997[Ishizaki et al, , 2000]. Therefore, we tested whether inhibition of p160ROCK by a highly-selective inhibitor, Y-27632, affected fibroblast cell motility in the presence of serum.…”

Section: Rhoa Activation Modulates Fibroblast Motility In Steady-statmentioning

confidence: 99%

The role of RhoA in the regulation of cell morphology and motility

Tkach¹,

Bock²,

Berezin³

2005

Cell Motil. Cytoskeleton

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Members of the Rho family of small GTPases are key regulators of the actin cytoskeleton, particularly in relation to the cell shape changes and the adhesion dynamic that drive cell migration. Here, we report the effect of activation or inhibition of the function of RhoA on cell motility and morphology. Both in the presence and the absence of serum, expression of constitutively active RhoA dramatically inhibited L929 fibroblasts' cell motility, and induced a rounding of the cells and a decrease in the number of processes per cell. In contrast, expression of a dominant negative mutant of RhoA had no effect on cell motility or morphology in steady-state conditions with or without serum in the medium. Inhibition of p160ROCK, a kinase effector of RhoA, only partially inhibited cell migration. Conversely, when cells were submitted to a period of serum deprivation followed by addition of serum, inhibition of endogenous RhoA by expression of the dominant negative mutant of RhoA impeded cell motility after serum stimulation. Thus, RhoA activity is required for stimulation of cell locomotion by serum factors. It was also observed that the addition of serum factors to quiescent L929 and NR6wtEGFR fibroblasts resulted in a delayed motility response of several hours compared to the immediately induced morphological changes, indicating the absence of a previously assumed direct correlation between changes in cell motility and cell morphology in response to serum addition. The motility response of L929 and NR6wtEGFR fibroblasts to serum stimulation required protein synthesis. Cell Motil.

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“…The small GTPase Rho and its target Rho-associated protein kinases (Rho kinase, p160ROCK) [9,18,19] control cell adhesion [10] and motility [35] through reorganization of the actin cytoskeleton and regulation of actomyosin contractility [3] in a number of cellular processes, including vascular contraction [31], tumor invasion [12], penile erection [2], and apoptosis [4]. Further, several lines of evidence indicated that Rho-ROCK signaling also has been involved in cellular transformation.…”

Section: Introductionmentioning

confidence: 99%

Stimulation of Ectopic Bone Formation in Response to BMP-2 by Rho Kinase Inhibitor: A Pilot Study

Yoshikawa

Yoshioka

Nakase

et al. 2009

Clin Orthop Relat Res

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The small GTPase Rho and Rho-associated protein kinase (Rho kinase, ROCK) signal participates in a variety of biological functions including vascular contraction, tumor invasion, and penile erection. Evidence also suggests Rho-ROCK is involved in signaling for mesenchymal cellular differentiation. However, whether it is involved in osteoblastic differentiation is unknown. We therefore asked whether Rho-ROCK signaling participates in recombinant human bone morphogenetic protein (rhBMP-2)-induced osteogenesis both in vitro and in vivo. Continuous delivery of a specific ROCK inhibitor (Y-27632) enhanced ectopic bone formation induced by rhBMP-2 impregnated into an atelocollagen carrier in mice without affecting systemic bone metabolism. Treatment with Y-27632 also enhanced the osteoblastic differentiation of cultured murine neonatal calvarial cells. These effects were associated with increased expression of BMP-4 gene. Expression of a dominant negative mutant of ROCK in ST2 cells promoted osteoblastic differentiation, while a constitutively active mutant of ROCK attenuated osteoblastic differentiation and the ROCK inhibitor reversed this phenotype. Thus, ROCK inhibits osteogenesis, and a ROCK inhibitor in combination with the local delivery of rhBMP/collagen composite may be clinically applicable for stimulating bone formation.

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p160^ROCK, a Rho‐associated coiled‐coil forming protein kinase, works downstream of Rho and induces focal adhesions

Cited by 481 publications

References 21 publications

Rho kinase in the regulation of cell death and survival

Rho kinase in the regulation of cell death and survival

The role of RhoA in the regulation of cell morphology and motility

Stimulation of Ectopic Bone Formation in Response to BMP-2 by Rho Kinase Inhibitor: A Pilot Study

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p160ROCK, a Rho‐associated coiled‐coil forming protein kinase, works downstream of Rho and induces focal adhesions

Cited by 481 publications

References 21 publications

Rho kinase in the regulation of cell death and survival

Rho kinase in the regulation of cell death and survival

The role of RhoA in the regulation of cell morphology and motility

Stimulation of Ectopic Bone Formation in Response to BMP-2 by Rho Kinase Inhibitor: A Pilot Study

Contact Info

Product

Resources

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p160^ROCK, a Rho‐associated coiled‐coil forming protein kinase, works downstream of Rho and induces focal adhesions