ArhGAP15, a novel human RacGAP protein with GTPase binding property.

Institute of Molecular and Cell Biology, Glaxo-IMCB Group, 30 Medical Drive, Singapore 117609, Republic of Singapore.
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.
Mesh Terms:
Amino Acid Sequence, Blood Proteins, GTP Phosphohydrolases, GTPase-Activating Proteins, Hela Cells, Humans, Hydrogen-Ion Concentration, Molecular Sequence Data, Phosphoproteins, Protein Binding, Protein Structure, Tertiary, rac1 GTP-Binding Protein
FEBS Lett. Mar. 27, 2003; 539(1);131-7 [PUBMED:12650940]
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