| Structural highlights
Function
[RGAP1_HUMAN] Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Plays key roles in controlling cell growth and differentiation of hematopoietic cells through mechanisms other than regulating Rac GTPase activity. Also involved in the regulation of growth-related processes in adipocytes and myoblasts. May be involved in regulating spermatogenesis and in the RACGAP1 pathway in neuronal proliferation. Shows strong GAP (GTPase activation) activity towards CDC42 and RAC1 and less towards RHOA. Essential for the early stages of embryogenesis. May play a role in regulating cortical activity through RHOA during cytokinesis. May participate in the regulation of sulfate transport in male germ cells.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12]
Publication Abstract from PubMed
Cytokinesis in animal cells relies on a centralspindlin complex consisting of male germ cell RacGap (MgcRacGAP) and mitotic kinesin-like protein 1 (MKLP1). Rho GTPases act as molecular switches to regulate the actin cytoskeleton for cytokinesis, of which Rac1 is regulated by MgcRacGAP. In this study, we determined the crystal structure of the GTPase-activating protein (GAP) domain of MgcRacGAP at a resolution of 1.9A. The conformation of Arg385, which is a key residue for GAP activity, was found to be different from that of previously reported GAP proteins, and MgcRacGAP (residues 348-546) was found to exist as a monomer in solution, according to Stokes radii. We also measured the GAP activity of MgcRacGAP mutants for Rac1.
Crystal structure of GTPase-activating domain from human MgcRacGAP.,Matsuura A, Lee HH Biochem Biophys Res Commun. 2013 Jun 7;435(3):367-72. doi:, 10.1016/j.bbrc.2013.04.094. Epub 2013 May 7. PMID:23665020[13]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kawashima T, Hirose K, Satoh T, Kaneko A, Ikeda Y, Kaziro Y, Nosaka T, Kitamura T. MgcRacGAP is involved in the control of growth and differentiation of hematopoietic cells. Blood. 2000 Sep 15;96(6):2116-24. PMID:10979956
- ↑ Toure A, Dorseuil O, Morin L, Timmons P, Jegou B, Reibel L, Gacon G. MgcRacGAP, a new human GTPase-activating protein for Rac and Cdc42 similar to Drosophila rotundRacGAP gene product, is expressed in male germ cells. J Biol Chem. 1998 Mar 13;273(11):6019-23. PMID:9497316
- ↑ Hirose K, Kawashima T, Iwamoto I, Nosaka T, Kitamura T. MgcRacGAP is involved in cytokinesis through associating with mitotic spindle and midbody. J Biol Chem. 2001 Feb 23;276(8):5821-8. Epub 2000 Nov 20. PMID:11085985 doi:http://dx.doi.org/10.1074/jbc.M007252200
- ↑ Toure A, Morin L, Pineau C, Becq F, Dorseuil O, Gacon G. Tat1, a novel sulfate transporter specifically expressed in human male germ cells and potentially linked to rhogtpase signaling. J Biol Chem. 2001 Jun 8;276(23):20309-15. Epub 2001 Mar 5. PMID:11278976 doi:http://dx.doi.org/10.1074/jbc.M011740200
- ↑ Mishima M, Kaitna S, Glotzer M. Central spindle assembly and cytokinesis require a kinesin-like protein/RhoGAP complex with microtubule bundling activity. Dev Cell. 2002 Jan;2(1):41-54. PMID:11782313
- ↑ Lee JS, Kamijo K, Ohara N, Kitamura T, Miki T. MgcRacGAP regulates cortical activity through RhoA during cytokinesis. Exp Cell Res. 2004 Feb 15;293(2):275-82. PMID:14729465
- ↑ Oceguera-Yanez F, Kimura K, Yasuda S, Higashida C, Kitamura T, Hiraoka Y, Haraguchi T, Narumiya S. Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis. J Cell Biol. 2005 Jan 17;168(2):221-32. Epub 2005 Jan 10. PMID:15642749 doi:10.1083/jcb.200408085
- ↑ Yuce O, Piekny A, Glotzer M. An ECT2-centralspindlin complex regulates the localization and function of RhoA. J Cell Biol. 2005 Aug 15;170(4):571-82. PMID:16103226 doi:10.1083/jcb.200501097
- ↑ Zhao WM, Fang G. MgcRacGAP controls the assembly of the contractile ring and the initiation of cytokinesis. Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13158-63. Epub 2005 Aug 29. PMID:16129829 doi:http://dx.doi.org/0504145102
- ↑ Kamijo K, Ohara N, Abe M, Uchimura T, Hosoya H, Lee JS, Miki T. Dissecting the role of Rho-mediated signaling in contractile ring formation. Mol Biol Cell. 2006 Jan;17(1):43-55. Epub 2005 Oct 19. PMID:16236794 doi:10.1091/mbc.E05-06-0569
- ↑ Burkard ME, Maciejowski J, Rodriguez-Bravo V, Repka M, Lowery DM, Clauser KR, Zhang C, Shokat KM, Carr SA, Yaffe MB, Jallepalli PV. Plk1 self-organization and priming phosphorylation of HsCYK-4 at the spindle midzone regulate the onset of division in human cells. PLoS Biol. 2009 May 5;7(5):e1000111. doi: 10.1371/journal.pbio.1000111. Epub 2009, May 26. PMID:19468302 doi:10.1371/journal.pbio.1000111
- ↑ Wolfe BA, Takaki T, Petronczki M, Glotzer M. Polo-like kinase 1 directs assembly of the HsCyk-4 RhoGAP/Ect2 RhoGEF complex to initiate cleavage furrow formation. PLoS Biol. 2009 May 5;7(5):e1000110. doi: 10.1371/journal.pbio.1000110. Epub 2009, May 26. PMID:19468300 doi:10.1371/journal.pbio.1000110
- ↑ Matsuura A, Lee HH. Crystal structure of GTPase-activating domain from human MgcRacGAP. Biochem Biophys Res Commun. 2013 Jun 7;435(3):367-72. doi:, 10.1016/j.bbrc.2013.04.094. Epub 2013 May 7. PMID:23665020 doi:http://dx.doi.org/10.1016/j.bbrc.2013.04.094
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