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RESEARCH ARTICLE |
1 Glaxo-IMCB Group, Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609
2 Membrane Biology Laboratory, Institute of Molecular and Cell Biology, Singapore 117609
3 Institute of Neurology, 1 Wakefield Street, London, WC1N 1PJ, UK
*Author for correspondence (e-mail: mcbkohcg{at}imcb.nus.edu.sg)
Accepted August 11, 2001
PIX is a Rho-family guanine nucleotide exchange factor that binds PAK. We previously described two isoforms of PIX that differ in their N termini. Here, we report the identification of a new splice variant of ßPIX, designated ß2PIX, that is the dominant species in brain and that lacks the region of 
120 residues with predicted coiled-coil structure at the C terminus of ß1PIX. Instead, ß2PIX contains a serine-rich C terminus. To determine whether these splice variants differ in their cellular function, we studied the effect of expressing these proteins in HeLa cells. We found that the coiled-coil region plays a key role in the localization of ß1PIX to the cell periphery and is also responsible for PIX dimerization. Overexpression of ß1, but not ß2PIX, drives formation of membrane ruffles and microvillus-like structures (via activation of Rac1 and Cdc42, respectively), indicating that its function requires localized activation of these GTPases. Thus, ß1PIX, like other RhoGEFs, exerts specific morphological functions that are dependent on its intracellular location and are mediated by its C-terminal dimerization domain.
Key words: GEF, GTPase, Rho family, PIX, PAK
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