3BP-1, an SH3 domain binding protein, has GAP activity for Rac and inhibits growth factor-induced membrane ruffling in fibroblasts

Abstract

The SH3 binding protein, 3BP‐1, was originally cloned as a partial cDNA from an expression library using the Abl SH3 domain as a probe. In addition to an SH3 binding domain, 3BP‐1 displayed homology to a class of GTPase activating proteins (GAPs) active against Rac and Rho proteins. We report here a full length cDNA of 3BP‐1 which extends the homology to GAP proteins previously noted. 3BP‐1 functions in vitro as a GAP with a specificity for Rac‐related G proteins. Microinjection of the 3BP‐1 protein into serum‐starved fibroblasts produces an inhibition of platelet‐derived growth factor (PDGF)‐induced membrane ruffling mediated by Rac. Co‐injection of 3BP‐1 with an activated Rac mutant that is unresponsive to GAPs, counter‐acts this inhibition. 3BP‐1 does not show in vitro activity towards Rho and, in agreement with this finding, microinjection of 3BP‐1 into fibroblasts has no effect on lysophosphatidic acid (LPA)‐induced stress fiber assembly mediated by Rho. Thus 3BP‐1 is a new and specific Rac GAP that can act in cells to counter Rac‐mediated membrane ruffling. How its SH3 binding site interacts with its GAP activity remains to be understood.

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