p21 Cdc42(rho-G)/Rac-associated kinase, PAK1, p65PAK or alpha-PAK

Function

• activated kinase acts on a variety of targets
• likely to be the GTPase effector that links the Rho-related GTPases to the JNK MAP kinase pathway
• activated by CDC42 & RAC1
• involved in dissolution of stress fibers & reorganization of focal complexes
• involved in regulation of microtubule biogenesis through phosphorylation of TBCB
• involved in regulation of signaling pathways involving MAPK8 & RELA
• activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 & CDC2L2
• activated by binding small G proteins
• binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, enables phosphorylation of Thr-423 & allows the kinase domain to adopt an active structure
• also activated by binding to GTP-bound CDC42, independent of phosphorylation state of Thr-423
• phosphorylation of Thr-84 by OXSR1 inhibits this activation (putative)
• homodimer in its autoinhibited state
• active as monomer
• interacts tightly with GTP-bound but not GDP-bound CDC42/P21 & RAC1
• binds to the caspase-cleaved p110 isoform of CDC2L1 & CDC2L2, p110C, but not the full-length proteins
• component of cytoplasmic complexes, which also contain PXN, ARHGEF6 & GIT1
• autophosphorylated when activated by CDC42/p21 & RAC1
• inhibited by PAK1IP1

ATP + a protein = ADP + a phosphoprotein

Cofactor: Mg+2

Expression

abundant in brain

More general terms

• p21 (CDKN1A)-activated kinase (PAK)

Database

• UniProt: http://www.uniprot.org/uniprot/Q13153.html
• OMIM: https://mirror.omim.org/entry/602590
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5058