IDENTIFICATION OF A NOVEL RAC1-INTERACTING PROTEIN INVOLVED IN MEMBRANE RUFFLING

The Rac GTP binding proteins are implicated in actin cytoskeleton-memb rane interaction in mammalian cells. In fibroblast cells, Rac has been shown to mediate growth factor-induced polymerization of actin to for m membrane ruffles and lamellipodia. We report here the isolation of a novel Rac1-interacting protein, POR1. POR1 binds directly to Rac1, an d the interaction of POR1 with Rac1 is GTP dependent. A mutation in th e Rad effector binding loop shown to abolish membrane ruffling also ab olishes interaction with POR1. Truncated versions of POR1 inhibit the induction of membrane ruffling by an activated mutant of Rac1, V12Rac1 , in quiescent rat embryonic fibroblast REF52 cells. Furthermore, POR1 synergizes with an activated mutant of Ras, V12Ras, in the induction of membrane ruffling. These results suggest a potential role for POR1 in Rac1-mediated signaling pathways.