Linked Life Data

20660160

Source:http://linkedlifedata.com/resource/pubmed/id/20660160

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2010-9-14
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1939-4586
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3232-46
pubmed:dateRevised
2011-3-18
pubmed:meshHeading
pubmed-meshheading:20660160-Amino Acid Sequence, pubmed-meshheading:20660160-Binding Sites, pubmed-meshheading:20660160-GTPase-Activating Proteins, pubmed-meshheading:20660160-Guanosine Diphosphate, pubmed-meshheading:20660160-Guanosine Triphosphate, pubmed-meshheading:20660160-HEK293 Cells, pubmed-meshheading:20660160-HeLa Cells, pubmed-meshheading:20660160-Humans, pubmed-meshheading:20660160-Molecular Sequence Data, pubmed-meshheading:20660160-Mutagenesis, Site-Directed, pubmed-meshheading:20660160-Protein Binding, pubmed-meshheading:20660160-Protein Structure, Tertiary, pubmed-meshheading:20660160-Recombinant Fusion Proteins, pubmed-meshheading:20660160-Schizosaccharomyces, pubmed-meshheading:20660160-Schizosaccharomyces pombe Proteins, pubmed-meshheading:20660160-Sequence Homology, Amino Acid, pubmed-meshheading:20660160-rhoA GTP-Binding Protein
pubmed:year
2010
pubmed:articleTitle
The BNIP-2 and Cdc42GAP homology (BCH) domain of p50RhoGAP/Cdc42GAP sequesters RhoA from inactivation by the adjacent GTPase-activating protein domain.
pubmed:affiliation
Cell Signaling and Developmental Biology Laboratory, Department of Biological Sciences, National University of Singapore, Singapore 117543, Republic of Singapore. dbszhouy@nus.edu.sg
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't