Rho-associated protein kinase 1

Definition:

Protein kinase which is a key regulator of the actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, TPPP, PFN1 and PPP1R12A. Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing. Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress. Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability (By similarity). Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Required for centrosome positioning and centrosome-dependent exit from mitosis (By similarity). Plays a role in terminal erythroid differentiation. Inhibits podocyte motility via regulation of actin cytoskeletal dynamics and phosphorylation of CFL1 (By similarity). Promotes keratinocyte terminal differentiation. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization (By similarity). May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles (By similarity).

References:

[1]. Alice V Schofield, et al. Tubulin polymerization promoting protein 1 (Tppp1) phosphorylation by Rho-associated coiled-coil kinase (rock) and cyclin-dependent kinase 1 (Cdk1) inhibits microtubule dynamics to increase cell proliferation. J Biol Chem. 2013 Mar 15;288(11):7907-7917. [Content Brief]

[2]. Jieya Shao, et al. Phosphorylation of profilin by ROCK1 regulates polyglutamine aggregation. Mol Cell Biol. 2008 Sep;28(17):5196-208. [Content Brief]

[3]. Laura Hagerty, et al. ROCK1 phosphorylates and activates zipper-interacting protein kinase. J Biol Chem. 2007 Feb 16;282(7):4884-4893. [Content Brief]

[4]. Frances E Lock, et al. Distinct roles for ROCK1 and ROCK2 in the regulation of keratinocyte differentiation. PLoS One. 2009 Dec 4;4(12):e8190. [Content Brief]

[5]. M Maekawa, et al. Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science. 1999 Aug 6;285(5429):895-8. [Content Brief]

[6]. M Sebbagh, et al. Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing. Nat Cell Biol. 2001 Apr;3(4):346-52. [Content Brief]

[7]. Yuepeng Wang, et al. ROCK isoform regulation of myosin phosphatase and contractility in vascular smooth muscle cells. Circ Res. 2009 Feb 27;104(4):531-40. [Content Brief]

[8]. T Sumi, et al. Specific activation of LIM kinase 2 via phosphorylation of threonine 505 by ROCK, a Rho-dependent protein kinase. J Biol Chem. 2001 Jan 5;276(1):670-6. [Content Brief]

[9]. Pat P Ongusaha, 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 Nov 25;1(47):ra14. [Content Brief]

[10]. K Ohashi, et al. Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop. J Biol Chem. 2000 Feb 4;275(5):3577-82. [Content Brief]

[11]. J E Van Eyk, et al. Different molecular mechanisms for Rho family GTPase-dependent, Ca2+-independent contraction of smooth muscle. J Biol Chem. 1998 Sep 4;273(36):23433-9. [Content Brief]

[12]. A-S Gabet, et al. Caspase-activated ROCK-1 allows erythroblast terminal maturation independently of cytokine-induced Rho signaling. Cell Death Differ. 2011 Apr;18(4):678-89. [Content Brief]

[13]. Sebastian Hannemann, et al. The Diaphanous-related Formin FHOD1 associates with ROCK1 and promotes Src-dependent plasma membrane blebbing. J Biol Chem. 2008 Oct 10;283(41):27891-27903. [Content Brief]

[14]. T Ishizaki, 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 Apr 15;15(8):1885-93. [Content Brief]

[15]. Jens Kroll, et al. Inhibition of Rho-dependent kinases ROCK I/II activates VEGF-driven retinal neovascularization and sprouting angiogenesis. Am J Physiol Heart Circ Physiol. 2009 Mar;296(3):H893-9. [Content Brief]

[16]. Alice V Schofield, et al. Rho-associated coiled-coil kinase (ROCK) protein controls microtubule dynamics in a novel signaling pathway that regulates cell migration. J Biol Chem. 2012 Dec 21;287(52):43620-9. [Content Brief]

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