ROCK‐I and ROCK‐II, two isoforms of Rho‐associated coiled‐coil forming protein serine/threonine kinase in mice

Nakagawa, Osamu; Fujisawa, Katsuki; Ishizaki, Toshimasa; Saito, Yuji; Nakao, Kazuwa; Narumiya, Shuh

doi:10.1016/0014-5793(96)00811-3

Cited by 694 publications

(598 citation statements)

References 16 publications

(11 reference statements)

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“…We demonstrated that adult NPCs express both isoforms of ROCK, namely ROCK1 and ROCK2. These isoforms share 65% protein homology and especially high conservation at the kinasebinding domain (92% homology) [52]. Because of this highsequence homology, development of an exclusively ROCK1 or ROCK2 inhibitor has proven to be difficult and most of the inhibitors currently available target both isoforms, therefore, the relative contributions of each isoform is difficult to determine.…”

Section: Regulation Of Npc Morphology and Migration By Rho Gtpase Sigmentioning

confidence: 99%

The Rho Kinase Pathway Regulates Mouse Adult Neural Precursor Cell Migration

et al. 2011

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Adult neural precursor cells (NPCs) in the subventricular zone (SVZ) normally migrate via the rostral migratory stream (RMS) to the olfactory bulb (OB). Following neural injury, they also migrate to the site of damage. This study investigated the role of Rho-dependent kinase (ROCK) on the migration of NPCs in vitro and in vivo. In vitro, using neurospheres or SVZ explants, inhibition of ROCK using Y27632 promoted cell body elongation, process protrusion, and migration, while inhibiting NPC chain formation. It had no effect on proliferation, apoptosis, or differentiation. Both isoforms of ROCK were involved. Using siRNA, knockdown of both ROCK1 and ROCK2 was required to promote NPC migration and morphological changes; knockdown of ROCK2 alone was partially effective, with little/no effect of knockdown of ROCK1 alone. In vivo, infusion of Y27632 plus Bromodeoxyuridine (BrdU) into the lateral ventricle for 1 week reduced the number of BrdU-labeled NPCs in the OB compared with BrdU infusion alone. However, ROCK inhibition did not affect the tangential-to-radial switch of NPC migration, as labeled cells were present in all OB layers. The decrease in NPC number at the OB was not attributed to a decrease in NPCs at the SVZ. However, ROCK inhibition decreased the density of BrdU-labeled cells in the RMS and increased the distribution of these cells to ectopic brain regions, such as the accessory olfactory nucleus, where the majority differentiated into neurons. These findings suggest that ROCK signaling regulates NPC migration via regulation of cell-cell contact and chain migration.

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Section: Regulation Of Npc Morphology and Migration By Rho Gtpase Sigmentioning

confidence: 99%

The Rho Kinase Pathway Regulates Mouse Adult Neural Precursor Cell Migration

et al. 2011

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“…ROCK was initially identified as a Rho-binding protein with serine/threonine protein kinase activity and with a molecular mass of about 160 kDa [54,73,82,95]. The protein contains a catalytic kinase domain at the amino terminus, followed by a central coiled-coil domain including a Rho-binding domain (RBD), and a carboxyl-terminal pleckstrin-homology (PH) domain with an internal cysteine-rich (CR) domain (Fig.…”

Section: Structure and Expression Of Rock Isoformsmentioning

confidence: 99%

“…One of the best-characterized effectors of Rho is Rho-associated coiled-coilcontaining protein kinase (hereafter referred to as ROCK), which was discovered in 1996 [54,73,82,95]. During the last decade, the Rho/ROCK signaling pathway has attracted much attention in various research fields, and more than 2,000 articles have been published; many of which focus on ROCK function in the cardiovascular system, central nervous system, cancers and embryonic development.…”

Section: Introductionmentioning

confidence: 99%

Rho kinase in the regulation of cell death and survival

Shi

Wei

2007

Arch. Immunol. Ther. Exp.

211

183

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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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“…Rho-associated coiled-coil kinases (ROCKs) were initially identified as Rho GTPase effectors (Nakagawa et al, 1996;Ishizaki et al, 1997;Bishop and Hall, 2000). Two members of the ROCK family, ROCK1 (ROK␤) and ROCK2 (ROK␣), have been identified thus far (Nakagawa et al, 1996;Amano et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…Two members of the ROCK family, ROCK1 (ROK␤) and ROCK2 (ROK␣), have been identified thus far (Nakagawa et al, 1996;Amano et al, 2000). These serine/ threonine kinases phosphorylate a large number of substrates, including cytoskeletal proteins, myosin light chain, LIM kinase, and myosin phosphatase (Nakagawa et al, 1996;Amano et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Rho‐associated kinases play an essential role in cardiac morphogenesis and cardiomyocyte proliferation

Zhao

Rivkees

2002

Developmental Dynamics

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Rho-associated coiled-coil kinases (ROCKs), initially identified as effectors for Rho GTPases, play a role in cardiac cell physiology and are also expressed in the developing heart. However, their role in cardiac development is not known. To investigate the role of these kinases in cardiac development, we examined cardiac development in cultured murine embryos treated with the ROCK inhibitor Y27632. After inhibition of ROCK activity, we found disturbed cardiac chamber formation and trabeculation. To further examine the mechanisms by which ROCK blockade causes cardiac hypoplasia, we assessed programmed cell death and cell proliferation in the hearts. We found decreased cell proliferation in the Y27632-treated hearts, but no changes in programmed cell death. We further observed that ROCK inhibition decreased cardiac myocyte proliferation, suggesting that ROCK kinases regulate cardiomyocyte division. To identify factors involved in ROCK action in regulation of cardiac cell division, we examined expression of cell cycle proteins by using Western blot analysis. We found that ROCK blockade decreased expression of cell cycle proteins, cyclin D3, CDK6, and p27 KIP1 in the hearts and cardiomyocytes, which are required for initiation of cell cycle and G1/S phase transition. These observations show that ROCK kinases play a role in cardiac development and that ROCK kinases regulate cardiac cell proliferation and cell cycle protein expression. Developmental Dynamics 226:24 -32, 2003.

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ROCK‐I and ROCK‐II, two isoforms of Rho‐associated coiled‐coil forming protein serine/threonine kinase in mice

Cited by 694 publications

References 16 publications

The Rho Kinase Pathway Regulates Mouse Adult Neural Precursor Cell Migration

The Rho Kinase Pathway Regulates Mouse Adult Neural Precursor Cell Migration

Rho kinase in the regulation of cell death and survival

Rho‐associated kinases play an essential role in cardiac morphogenesis and cardiomyocyte proliferation

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