Please use this identifier to cite or link to this item: https://doi.org/10.1091/mbc.E09-05-0408
Title: The BNIP-2 and Cdc42GAP Homology (BCH) domain of p50RhoGAP/Cdc42GAP sequesters RhoA from inactivation by the adjacent GTPase-activating protein domain
Authors: Zhou, Y.T. 
Chew, L.L. 
Lin, S.-C.
Low, B.C. 
Issue Date: 15-Sep-2010
Citation: Zhou, Y.T.,Chew, L.L.,Lin, S.-C.,Low, B.C. (2010-09-15). The BNIP-2 and Cdc42GAP Homology (BCH) domain of p50RhoGAP/Cdc42GAP sequesters RhoA from inactivation by the adjacent GTPase-activating protein domain. Molecular Biology of the Cell 21 (18) : 3232-3246. ScholarBank@NUS Repository. https://doi.org/10.1091/mbc.E09-05-0408
Abstract: The BNIP-2 and Cdc42GAP homology (BCH) domain is a novel regulator for Rho GTPases, but its impact on p50-Rho GTPase-activating protein (p50RhoGAP or Cdc42GAP) in cells remains elusive. Here we show that deletion of the BCH domain from p50RhoGAP enhanced its GAP activity and caused drastic cell rounding. Introducing constitutively active RhoA or inactivating GAP domain blocked such effect, whereas replacing the BCH domain with endosome-targeting. SNX3 excluded requirement of endosomal localization in regulating the GAP activity. Substitution with homologous BCH domain from Schizosaccharomyces pombe, which does not bind mammalian RhoA, also led to complete loss of suppression. Interestingly, the p50RhoGAP BCH domain only targeted RhoA, but not Cdc42 or Rac1, and it was unable to distinguish between GDP and the GTP-bound form of RhoA. Further mutagenesis revealed a RhoA-binding motif (residues 85-120), which when deleted, significantly reduced BCH inhibition on GAP-mediated cell rounding, whereas its full suppression also required an intramolecular interaction motif (residues 169-197). Therefore, BCH domain serves as a local modulator in cis to sequester RhoA from inactivation by the adjacent GAP domain, adding to a new paradigm for regulating p50RhoGAP signaling. © 2010 Y. T. Zhou et al.
Source Title: Molecular Biology of the Cell
URI: http://scholarbank.nus.edu.sg/handle/10635/101870
ISSN: 10591524
DOI: 10.1091/mbc.E09-05-0408
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