Three recently identified isoforms of serine/threonine kinases, designated αPAK p68, βPAK p65 and γPAK p62, have been shown to exhibit a high degree of sequence homology with the S. cerevisiae kinase STE20, involved in pheromone signaling. The α, β, and γPAK isoforms complex specifically with Rac1 and Cdc42 in their active GTP bound state, inhibiting their intrinsic GTPase activity leading to their autophosphorylation. 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 MEK4 which is involved in the JNK signaling pathway. While the PAK isoforms interact in a GTP-dependent manner with Rac1 and Cdc42, they do not interact with Rho.
