| Modification Notes |
Three isoforms of serine/threonine kinases, designated aPAK p68, bPAK p65 and gPAK p62, have been shown to exhibit a high degree of sequence homol-ogy with the S. cerevisiae kinase Ste 20, involved in pheromone signaling. The a, b and gPAK 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 gPAK, including Ser 19, Ser 141 and Thr 402, and phosphorylation of Ser 141 and Thr 402 is correlated with gPAK activation. 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. |