title: ArhGAP15, a novel human RacGAP protein with GTPase binding property.
abstract: We have previously described a partial cDNA sequence encoding a RhoGAP protein, GAP25 that is homologous to the recently reported ArhGAP9 and ArhGAP12. We now describe a related new member ArhGAP15 that shares a number of domain similarities, including a pleckstrin homology (PH) domain, a RhoGAP domain and a novel motif N-terminal to the GAP domain. This novel motif was found to be responsible for nucleotide-independent Rac1 binding. Using swop mutants of Rac/Cdc42, we have established that the binding is through the C-terminal half of Rac1. The GAP domain of ArhGAP15 showed specificity towards Rac1 in vitro. The PH domain is required for ArhGAP15 to localize to cell periphery and over-expression of the full-length ArhGAP15, but not the mutant with a partial deletion of the PH domain, resulted in an increase in actin stress fibers and cell contraction. These morphological effects can be attenuated by the co-expression of dominant negative Rac1(N17). HeLa cells expressing ArhGAP15 were also resistant to phorbol myristatate acetate treatment, suggesting that ArhGAP15 is a potential regulator of Rac1.
authors.affiliation: Institute of Molecular and Cell Biology, Glaxo-IMCB Group, 30 Medical Drive, Singapore 117609, Republic of Singapore.
authors.forename: Mui Leng
authors.initials: ML
authors.lastname: Seoh
authors.forename: Chong Han
authors.initials: CH
authors.lastname: Ng
authors.forename: Jeffery
authors.initials: J
authors.lastname: Yong
authors.forename: Louis
authors.initials: L
authors.lastname: Lim
authors.forename: Thomas
authors.initials: T
authors.lastname: Leung
mesh_terms: D000595:Amino Acid Sequence; D001798:Blood Proteins / Q000737:chemistry; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: C473316:ARHGAP15 protein, human; D001798:Blood Proteins; D020690:GTPase-Activating Proteins; D010750:Phosphoproteins; C039077:platelet protein P47; C085379:rho GTPase-activating protein; D020558:GTP Phosphohydrolases; D020830:rac1 GTP-Binding Protein