| Structural highlights
6bca is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | GSP, MG |
| Gene: | RHOA, ARH12, ARHA, RHO12 (HUMAN), AKAP13, BRX, HT31, LBC (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[RHOA_HUMAN] Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion. Serves as a target for the yopT cysteine peptidase from Yersinia pestis, vector of the plague, and Yersinia pseudotuberculosis, which causes gastrointestinal disorders. Stimulates PKN2 kinase activity. May be an activator of PLCE1. Activated by ARHGEF2, which promotes the exchange of GDP for GTP. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization.[1] [2] [3] [4] [5] [6] [7] [8] [AKP13_HUMAN] Anchors cAMP-dependent protein kinase (PKA) and acts as an adapter protein to selectively couple G alpha-13 and Rho. Augments gene activation by the estrogen receptor in an element-specific and ligand-dependent manner. Activates estrogen receptor beta by a p38 MAPK-dependent pathway. Stimulates exchange activity on Rho proteins in vitro, but not on CDC42, Ras or Rac and may bind calcium ions.[9] [10] [11] [12]
Publication Abstract from PubMed
The Pleckstrin homology (PH) domains from the Lbc family of Rho Guanine Nucleotide Exchange Factors (Lbc RhoGEFs) interact with activated Rho family GTPases. All 7 Lbc RhoGEFs associate directly with activated Rho GTPases via their PH domains. However, the binding affinities between the PH domains and the GTPases vary greatly. Here we present two crystal structures at resolutions of 1.4A and 2.0A of RhoA complexed with the PH domain from p114RhoGEF (PDB access code 6BCB) and AKAP-LbcRhoGEF (PDB access code 6BCA), respectively. These high resolution structures, together with the earlier structures of PDZRhoGEF-PH.RhoA and p190RhoGEF-PH.RhoA complexes, identify a highly conserved interface between the PH domains from Lbc-RhoGEFs and activated Rho GTPases. This manuscript is related to the manuscript titled "Direct Regulation of p190RhoGEF by Activated Rho and Rac GTPases" published in the Journal of Structural Biology.
Crystal structures of the PH domains from Lbc family of RhoGEFs bound to activated RhoA GTPase.,Chen Z, Gutowski S, Sternweis PC Data Brief. 2018 Feb 20;17:356-362. doi: 10.1016/j.dib.2018.01.024. eCollection, 2018 Apr. PMID:29876405[13]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Quilliam LA, Lambert QT, Mickelson-Young LA, Westwick JK, Sparks AB, Kay BK, Jenkins NA, Gilbert DJ, Copeland NG, Der CJ. Isolation of a NCK-associated kinase, PRK2, an SH3-binding protein and potential effector of Rho protein signaling. J Biol Chem. 1996 Nov 15;271(46):28772-6. PMID:8910519
- ↑ Vincent S, Settleman J. The PRK2 kinase is a potential effector target of both Rho and Rac GTPases and regulates actin cytoskeletal organization. Mol Cell Biol. 1997 Apr;17(4):2247-56. PMID:9121475
- ↑ Wing MR, Snyder JT, Sondek J, Harden TK. Direct activation of phospholipase C-epsilon by Rho. J Biol Chem. 2003 Oct 17;278(42):41253-8. Epub 2003 Aug 4. PMID:12900402 doi:https://dx.doi.org/10.1074/jbc.M306904200
- ↑ 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
- ↑ 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
- ↑ Bristow JM, Sellers MH, Majumdar D, Anderson B, Hu L, Webb DJ. The Rho-family GEF Asef2 activates Rac to modulate adhesion and actin dynamics and thereby regulate cell migration. J Cell Sci. 2009 Dec 15;122(Pt 24):4535-46. doi: 10.1242/jcs.053728. Epub 2009, Nov 24. PMID:19934221 doi:10.1242/jcs.053728
- ↑ Zaoui K, Benseddik K, Daou P, Salaun D, Badache A. ErbB2 receptor controls microtubule capture by recruiting ACF7 to the plasma membrane of migrating cells. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18517-22. doi:, 10.1073/pnas.1000975107. Epub 2010 Oct 11. PMID:20937854 doi:10.1073/pnas.1000975107
- ↑ Wallace SW, Magalhaes A, Hall A. The Rho target PRK2 regulates apical junction formation in human bronchial epithelial cells. Mol Cell Biol. 2011 Jan;31(1):81-91. doi: 10.1128/MCB.01001-10. Epub 2010 Oct 25. PMID:20974804 doi:10.1128/MCB.01001-10
- ↑ Diviani D, Soderling J, Scott JD. AKAP-Lbc anchors protein kinase A and nucleates Galpha 12-selective Rho-mediated stress fiber formation. J Biol Chem. 2001 Nov 23;276(47):44247-57. Epub 2001 Sep 6. PMID:11546812 doi:https://dx.doi.org/10.1074/jbc.M106629200
- ↑ Rubino D, Driggers P, Arbit D, Kemp L, Miller B, Coso O, Pagliai K, Gray K, Gutkind S, Segars J. Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action. Oncogene. 1998 May 14;16(19):2513-26. PMID:9627117 doi:https://dx.doi.org/10.1038/sj.onc.1201783
- ↑ Sterpetti P, Hack AA, Bashar MP, Park B, Cheng SD, Knoll JH, Urano T, Feig LA, Toksoz D. Activation of the Lbc Rho exchange factor proto-oncogene by truncation of an extended C terminus that regulates transformation and targeting. Mol Cell Biol. 1999 Feb;19(2):1334-45. PMID:9891067
- ↑ Driggers PH, Segars JH, Rubino DM. The proto-oncoprotein Brx activates estrogen receptor beta by a p38 mitogen-activated protein kinase pathway. J Biol Chem. 2001 Dec 14;276(50):46792-7. Epub 2001 Sep 28. PMID:11579095 doi:https://dx.doi.org/10.1074/jbc.M106927200
- ↑ Chen Z, Gutowski S, Sternweis PC. Crystal structures of the PH domains from Lbc family of RhoGEFs bound to activated RhoA GTPase. Data Brief. 2018 Feb 20;17:356-362. doi: 10.1016/j.dib.2018.01.024. eCollection, 2018 Apr. PMID:29876405 doi:https://dx.doi.org/10.1016/j.dib.2018.01.024
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