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 βPIX, designated β2PIX, 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 β1PIX. Instead, β2PIX 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 β1PIX to the cell periphery and is also responsible for PIX dimerization. Overexpression of β1, but not β2PIX, 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, β1PIX, like other RhoGEFs, exerts specific morphological functions that are dependent on its intracellular location and are mediated by its C-terminal dimerization domain.

Keywords:
GEF, GTPase, Rho family, PIX, PAK
© The Company of Biologists Limited 2001
2001
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