| Structural highlights
Function
[SHRM2_HUMAN] May be involved in endothelial cell morphology changes during cell spreading. In the retinal pigment epithelium, may regulate the biogenesis of melanosomes and promote their association with the apical cell surface by inducing gamma-tubulin redistribution (By similarity). [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
Shroom-mediated remodeling of the actomyosin cytoskeleton is a critical driver of cellular shape and tissue morphology that underlies the development of many tissues, including the neural tube, eye, intestines, and vasculature. Shroom uses a conserved SD2 domain to direct the subcellular localization of Rho-kinase (Rock) which in turn drives changes in the cytoskeleton and cellular morphology through its ability to phosphorylate and activate non-muscle myosin II. Here, we present the structure of the human Shroom-Rock binding module, revealing an unexpected stoichiometry for Shrm in which two Shrm SD2 domains bind independent surfaces on Rock. Mutation of interfacial residues impaired Shroom-Rock binding in vitro, and resulted in altered remodeling of the cytoskeleton and loss of Shroom-mediated changes in cellular morphology. Additionally, we provide the first direct evidence that Shroom can function as a Rock activator. These data provide molecular insight into the Shroom-Rock interface and demonstrate that Shroom directly participates in regulating cytoskeletal dynamics, adding to its known role in Rock localization.
Structure of the Shroom-Rho kinase complex reveals a binding interface with monomeric Shroom that regulates cell morphology and stimulates kinase activity.,Zalewski JK, Mo JH, Heber S, Heroux A, Gardner RG, Hildebrand JD, VanDemark AP J Biol Chem. 2016 Oct 10. pii: jbc.M116.738559. PMID:27758857[15]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
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- ↑ 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
- ↑ Zalewski JK, Mo JH, Heber S, Heroux A, Gardner RG, Hildebrand JD, VanDemark AP. Structure of the Shroom-Rho kinase complex reveals a binding interface with monomeric Shroom that regulates cell morphology and stimulates kinase activity. J Biol Chem. 2016 Oct 10. pii: jbc.M116.738559. PMID:27758857 doi:http://dx.doi.org/10.1074/jbc.M116.738559
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