The serine/threonine kinase, p21 activated kinase (PAK), is a downstream effector of the small GTPases Cdc42 and Rac. PAK associates with Nck, the p85 and p110 subunits of PI3-kinase and PIX (PAK-interacting exchange factor) in a focal complex. The binding of PIX is necessary for the localization and activation of PAK in the Cdc42 to Rac signaling pathway, and this binding occurs through the high affinity of the N-terminal SH3 domain of PIX for a conserved proline rich PAK sequence. PIX exists as two isoforms, ? and ?, and both are highly expressed in heart, muscle and thymus tissues of human and rat. ?PIX is phosphorylated via PDGF and EphB2 receptor signaling pathways or through association with PI3-kinase. The ?PIX isoform predominantly acts as a guanine nucleotide exchange factor (GEF) on Rac, which may mediate lamellipodia formation.