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 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 gammaPAK, including Ser 19, Ser 141 and Thr 402, and phosphorylation of Ser 141 and Thr 402 is correlated with gammaPAK activation. Once phosphorylated and their affinity for Rac/Cdc42 reduced, the PAK isoforms disassociate from the complex to seek downstream substrates.
activated protein kinase alpha; Alpha-PAK; C-t-PAK2; CDC42/RAC effector kinase PAK-A; Gamma-PAK; OPHN3; p21 (CDKN1A)-activated kinase 1; p21 (CDKN1A)-activated kinase 2; p21 protein (Cdc42/Rac)-activated kinase 1; p21 protein (Cdc42/Rac)-activated kinase 2; p21-activated kinase 1; p21-activated kinase 2; p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast); p21/Cdc42/Rac1-activated kinase 1 (yeast Ste20-related); p27; p34; p58; p65-PAK; p68-PAK; PAK alpha; PAK beta; PAK-1; PAK-2; PAK-2p27; PAK-2p34; PAK3; PAK65; Protein kinase MUK2; S6/H4 kinase; Serine/threonine-protein kinase PAK 1; Serine/threonine-protein kinase PAK 2; STE20 homolog, yeast