ArhGAP15, a novel human RacGAP protein with GTPase binding property

FEBS Letters

Ng, Chong Han¹  Leung, Thomas¹  Lim, Louis¹  Seoh, Mui Leng¹  Yong, Jeffery¹ 

[1] From the Glaxo-IMCB Group, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609, Singapore

关键词: Rac1;    GAP;    Rac1-binding;    Actin cytoskeleton;    ABR;    active breakpoint cluster region gene product related protein;    BD;    p21-binding domain;    GAP;    GTPase activating protein;    PCR;    polymerase chain reaction;    PAK;    p21-activated kinase;    PH;    pleckstrin homology;    PMA;    phorbol myristatate acetate;   

DOI  :  10.1016/S0014-5793(03)00213-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown