| Structural highlights
Function
ROCK1_HUMAN Protein kinase which is a key regulator of 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, 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. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Required for centrosome positioning and centrosome-dependent exit from mitosis. Plays a role in terminal erythroid differentiation. May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles. Promotes keratinocyte terminal differentiation.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]
Publication Abstract from PubMed
Rho-associated coiled coil containing protein kinase (Rho-kinase or Rock) is a well-defined determinant of actin organization and dynamics in most animal cells characterized to date. One of the primary effectors of Rock is non-muscle myosin II. Activation of Rock results in increased contractility of myosin II and subsequent changes in actin architecture and cell morphology. The regulation of Rock is thought to occur via autoinhibition of the kinase domain via intramolecular interactions between the N-terminus and the C-terminus of the kinase. This autoinhibited state can be relieved via proteolytic cleavage, binding of lipids to a Pleckstrin Homology domain near the C-terminus, or binding of GTP-bound RhoA to the central coiled-coil region of Rock. Recent work has identified the Shroom family of proteins as an additional regulator of Rock either at the level of cellular distribution or catalytic activity or both. The Shroom-Rock complex is conserved in most animals and is essential for the formation of the neural tube, eye, and gut in vertebrates. To address the mechanism by which Shroom and Rock interact, we have solved the structure of the coiled-coil region of Rock that binds to Shroom proteins. Consistent with other observations, the Shroom binding domain is a parallel coiled-coil dimer. Using biochemical approaches, we have identified a large patch of residues that contribute to Shrm binding. Their orientation suggests that there may be two independent Shrm binding sites on opposing faces of the coiled-coil region of Rock. Finally, we show that the binding surface is essential for Rock colocalization with Shroom and for Shroom-mediated changes in cell morphology.
Structure of a highly conserved domain of Rock1 required for Shroom-mediated regulation of cell morphology.,Mohan S, Das D, Bauer RJ, Heroux A, Zalewski JK, Heber S, Dosunmu-Ogunbi AM, Trakselis MA, Hildebrand JD, Vandemark AP PLoS One. 2013 Dec 9;8(12):e81075. doi: 10.1371/journal.pone.0081075. eCollection, 2013. PMID:24349032[15]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ishizaki T, Maekawa M, Fujisawa K, Okawa K, Iwamatsu A, Fujita A, Watanabe N, Saito Y, Kakizuka A, Morii N, Narumiya S. 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. PMID:8617235
- ↑ Van Eyk JE, Arrell DK, Foster DB, Strauss JD, Heinonen TY, Furmaniak-Kazmierczak E, Cote GP, Mak AS. Different molecular mechanisms for Rho family GTPase-dependent, Ca2+-independent contraction of smooth muscle. J Biol Chem. 1998 Sep 4;273(36):23433-9. PMID:9722579
- ↑ Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, Obinata T, Ohashi K, Mizuno K, Narumiya S. Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science. 1999 Aug 6;285(5429):895-8. PMID:10436159
- ↑ 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 Feb 4;275(5):3577-82. PMID:10652353
- ↑ Sumi T, Matsumoto K, Nakamura T. 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. PMID:11018042 doi:10.1074/jbc.M007074200
- ↑ Sebbagh M, Renvoize 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 Apr;3(4):346-52. PMID:11283607 doi:10.1038/35070019
- ↑ Hagerty L, Weitzel DH, Chambers J, Fortner CN, Brush MH, Loiselle D, Hosoya H, Haystead TA. ROCK1 phosphorylates and activates zipper-interacting protein kinase. J Biol Chem. 2007 Feb 16;282(7):4884-93. Epub 2006 Dec 8. PMID:17158456 doi:10.1074/jbc.M609990200
- ↑ Hannemann S, Madrid R, Stastna J, Kitzing T, Gasteier J, Schonichen A, Bouchet J, Jimenez A, Geyer M, Grosse R, Benichou S, Fackler OT. The Diaphanous-related Formin FHOD1 associates with ROCK1 and promotes Src-dependent plasma membrane blebbing. J Biol Chem. 2008 Oct 10;283(41):27891-903. doi: 10.1074/jbc.M801800200. Epub, 2008 Aug 11. PMID:18694941 doi:10.1074/jbc.M801800200
- ↑ Shao J, Welch WJ, Diprospero NA, Diamond MI. Phosphorylation of profilin by ROCK1 regulates polyglutamine aggregation. Mol Cell Biol. 2008 Sep;28(17):5196-208. doi: 10.1128/MCB.00079-08. Epub 2008 Jun, 23. PMID:18573880 doi:10.1128/MCB.00079-08
- ↑ Ongusaha PP, Qi HH, Raj L, Kim YB, Aaronson SA, Davis RJ, Shi Y, Liao JK, Lee SW. 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. doi: 10.1126/scisignal.1161938. PMID:19036714 doi:10.1126/scisignal.1161938
- ↑ Kroll J, Epting D, Kern K, Dietz CT, Feng Y, Hammes HP, Wieland T, Augustin HG. 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. doi:, 10.1152/ajpheart.01038.2008. Epub 2009 Jan 30. PMID:19181962 doi:10.1152/ajpheart.01038.2008
- ↑ Wang Y, Zheng XR, Riddick N, Bryden M, Baur W, Zhang X, Surks HK. ROCK isoform regulation of myosin phosphatase and contractility in vascular smooth muscle cells. Circ Res. 2009 Feb 27;104(4):531-40. doi: 10.1161/CIRCRESAHA.108.188524. Epub, 2009 Jan 8. PMID:19131646 doi:10.1161/CIRCRESAHA.108.188524
- ↑ Lock FE, Hotchin NA. Distinct roles for ROCK1 and ROCK2 in the regulation of keratinocyte differentiation. PLoS One. 2009 Dec 4;4(12):e8190. doi: 10.1371/journal.pone.0008190. PMID:19997641 doi:10.1371/journal.pone.0008190
- ↑ Gabet AS, Coulon S, Fricot A, Vandekerckhove J, Chang Y, Ribeil JA, Lordier L, Zermati Y, Asnafi V, Belaid Z, Debili N, Vainchenker W, Varet B, Hermine O, Courtois G. Caspase-activated ROCK-1 allows erythroblast terminal maturation independently of cytokine-induced Rho signaling. Cell Death Differ. 2011 Apr;18(4):678-89. doi: 10.1038/cdd.2010.140. Epub 2010, Nov 12. PMID:21072057 doi:10.1038/cdd.2010.140
- ↑ Mohan S, Das D, Bauer RJ, Heroux A, Zalewski JK, Heber S, Dosunmu-Ogunbi AM, Trakselis MA, Hildebrand JD, Vandemark AP. Structure of a highly conserved domain of Rock1 required for Shroom-mediated regulation of cell morphology. PLoS One. 2013 Dec 9;8(12):e81075. doi: 10.1371/journal.pone.0081075. eCollection, 2013. PMID:24349032 doi:http://dx.doi.org/10.1371/journal.pone.0081075
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