Three isoforms of serine/threonine kinases, designated (alpha)PAK p68, (beta)PAK p65 and (gamma)PAK p62, have been shown to exhibit a high degree of sequence homology with the S. cerevisiae kinase Ste 20, involved in pheromone signaling. The (alpha), (beta) and (gamma)PAK isoforms complex specifically with Rac1 and Cdc42 in their active GTP-bound state, inhibiting their intrinsic GTPase activity leading to their autophosphorylation. There are eight sites of autophosphorylation on (gamma)PAK, including Ser 19, Ser 141 and Thr 402, and phosphorylation of Ser 141 and Thr 402 is correlated with (gamma)PAK activation. Once phosphorylated and their affinity for Rac/Cdc42 reduced, the PAK isoforms disassociate from the complex to seek downstream substrates.