5irc
p190A GAP domain complex with RhoAp190A GAP domain complex with RhoA
Structural highlights
Function[RHG35_RAT] Represses transcription of the glucocorticoid receptor by binding to the cis-acting regulatory sequence 5'-GAGAAAAGAAACTGGAGAAACTC-3'. May transduce signals from p21-ras to the nucleus, acting via the ras GTPase-activating protein (GAP). May also act as a tumor suppressor (By similarity). [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] Publication Abstract from PubMedRho GTPase-activating proteins (RhoGAPs) are one of the major classes of regulators of the Rho-related protein family that are crucial in many cellular processes, motility, contractility, growth, differentiation, and development. Using database searches we extracted 66 distinct human RhoGAPs, from which 57 have got a common catalytic domain capable of terminating Rho protein signaling by stimulating the slow intrinsic GTP hydrolysis (GTPase) reaction. The specificity of the majority of the members of RhoGAP family is largely uncharacterized. Here, we comprehensively investigated the sequence-structure-function relationship between RhoGAPs and Rho proteins by combining our in vitro data with in silico data. The activity of 14 representatives of the RhoGAP family towards 12 Rho family proteins was determined in real-time. We identified and structurally verified hotspots in the interface between RhoGAPs and Rho proteins as critical determinants for binding and catalysis. We have found that the RhoGAP domain itself is nonselective and in some cases rather inefficient under cell-free conditions. Thus, we propose that other domains of RhoGAPs confer substrate specificity and fine-tune their catalytic efficiency in cells. Deciphering the molecular and functional basis of RhoGAP family proteins: A systematic approach towards selective inactivation of Rho family proteins.,Amin E, Jaiswal M, Derewenda U, Reis K, Nouri K, Koessmeier KT, Aspenstrom P, Somlyo AV, Dvorsky R, Ahmadian MR J Biol Chem. 2016 Aug 1. pii: jbc.M116.736967. PMID:27481945[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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