RAC GTPASE INTERACTS WITH GAPS AND TARGET PROTEINS THROUGH MULTIPLE EFFECTOR SITES

Rac, a small GTPase in the ras superfamily, regulates at least two bio logical processes in animal cells: (i) the polymerization of actin and the assembly of integrin complexes to produce lamellipodia and ruffle s; and (ii) the activity of an NADPH oxidase in phagocytic cells. NADP H oxidase activation is mediated through a rac effector protein, p67(p hox), and using chimeras made between rac and the closely related GTPa se, rho, we have identified two distinct effector sites in rac, one N- terminal and one C-terminal, both of which are required for activation of p67(phox). The same two effector sites are essential far rac-induc ed actin polymerization in fibroblasts. p65(PAK), a ubiquitous serine/ threonine kinase, interacts with rac at both the N- and C-terminal eff ector sites, but the GTPase-activating protein, bcr interacts with rac at a different region, This makes p65(PAK), but not bcr, a candidate effector of rac-induced lamellipodium formation.