Three isoforms of Serine/Threonine kinases, designated alphaPAK p68, betaPAK p65 and gammaPAK 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 gammaPAK isoforms complex specifically with Rac 1 and Cdc42 in their active GTP-bound state, inhibiting their intrinsic GTPase activity leading to their autophosphorylation. The site of autophosphorylation on αPAK is Thr 423, which is in the kinase activation loop. Once phosphorylated and their affinity for Rac/Cdc42 reduced, the PAK isoforms disassociate from the complex to seek downstream substrates. One such putative substrate is MEK kinase, an upstream effector of MEK-4 which is involved in the JNK signaling pathway. While the PAK isoforms interact in a GTP-dependent manner with Rac 1 and Cdc42, they do not interact with Rho.Synonyms: Alpha-PAK, Gamma-PAK, PAK 1, PAK 2, PAK alpha, PAK gamma, PAK-1, PAK-2, PAK65, Serine/threonine-protein kinase PAK 1, Serine/threonine-protein kinase PAK 2, p21-activated kinase 1, p21-activated kinase 2, p58, p65-PAK