PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization ofthe actin cytoskeleton and in the formation of filopodia

The GTPases Rac and Cdc42Hs control diverse cellular functions. In addition to being mediators of intracellular signaling cascades, they have importan t roles in cell morphogenesis and mitogenesis. We have identified a novel P AK-related kinase, PAK4, as a new effector molecule for Cdc42Hs. PAK4 inter acts only with the activated form of Gdc42Hs through its GTPase-binding dom ain (GBD). Go-expression of PAK4 and the constitutively active Cdc42HsV12 c auses the redistribution of PAK4 to the brefeldin A-sensitive compartment o f the Golgi membrane and the subsequent induction of filopodia and actin po lymerization. Importantly, the reorganization of the actin cytoskeleton is dependent on PAK4 kinase activity and on its interaction with Cdc42Hs. Thus , unlike other members of the PAK family, PAK4 provides a novel link betwee n Cdc42Hs and the actin cytoskeleton. The cellular locations of PAK4 and Cd c42Hs suggest a role for the Golgi in cell morphogenesis.