| Modification Notes |
p21-activated kinases (PAK) are serine/threonine kinases that link Rho GTPases to cytoskeletal reorganization and nuclear signaling. Three common isoforms are åPAK p68, ∫PAK p65 and ©PAK p62. å, ∫ and ©PAK isoforms associate with Rac 1 and Cdc42 in their active GTP-bound state, inhibiting their intrinsic GTPase activity and mediating their autophosphorylation. ©PAK can undergo phosphorylation on Ser-19, Ser-141 and Thr-402, and phosphorylation of Ser-141 and Thr-402 correlates with ©PAK activation. Autophosphorylation of åPAK Thr-423 (Thr-402 for ∫PAK and Thr-421 for ©PAK) is catalyzed by Cdc42 and is required for kinase activation of PAK. Once phosphorylated and their affinity for Rac/Cdc42 reduced, PAK isoforms disassociate from the complex to seek downstream substrates. One such substrate is MEK kinase, an upstream effector of MEK4 which is involved in the JNK signaling pathway. |