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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 [1]
- 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
General
p21 (CDKN1A)-activated kinase (PAK)
Properties
SIZE: MW = 61 kD
entity length = 545 aa
STATE: active state
MOTIF: CRIB domain {75-88}
MOTIF: Thr phosphorylation site {T84}
Linker {89-269}
MOTIF: Ser phosphorylation site {S220}
kinase domain
SITE: 270-521
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 276-284
ATP-binding site
NAME: ATP-binding site
SITE: 299-299
aspartate residue {D389}
Database Correlations
OMIM 602590
UniProt Q13153
PFAM correlations
Entrez Gene 5058
References
- Manser E et al
A non-receptor tyrosine kinase that inhibits GTPase activity
of p21cdc42.
Nature 363:364 1993
PMID: 8497321
- UniProt :accession Q13153