PAK2

The p21 activated kinases (PAK) are critical effectors that link Rho GTPases to cytoskeleton reorganization and nuclear signaling. The PAK proteins are a family of serine/threonine kinases that serve as targets for the small GTP binding proteins, CDC42 and RAC1, and have been implicated in a wide range of biological activities. The protein encoded by this gene is activated by proteolytic cleavage during caspase-mediated apoptosis, and may play a role in regulating the apoptotic events in the dying cell. [provided by RefSeq, Jul 2008]

Full Name

P21 (RAC1) Activated Kinase 2

Function

Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation. Acts as downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Full-length PAK2 stimulates cell survival and cell growth. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Phosphorylates JUN and plays an important role in EGF-induced cell proliferation. Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP. Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis. On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway. Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation.

Biological Process

Adherens junction assemblyManual Assertion Based On ExperimentIMP:ARUK-UCL
Apoptotic processIEA:UniProtKB-KW
Bicellular tight junction assemblyManual Assertion Based On ExperimentIMP:ARUK-UCL
Cardiac muscle hypertrophyIEA:Ensembl
Cellular response to organic cyclic compoundIEA:Ensembl
Cellular response to transforming growth factor beta stimulusIEA:Ensembl
Dendritic spine developmentIEA:Ensembl
Intracellular signal transductionManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosisManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of protein kinase activityManual Assertion Based On ExperimentTAS:ProtInc
Negative regulation of stress fiber assemblyManual Assertion Based On ExperimentIMP:ARUK-UCL
Peptidyl-serine phosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
PhosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of extrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of peptidyl-tyrosine phosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
Protein autophosphorylationManual Assertion Based On ExperimentIDA:MGI
Protein localization to cell-cell junctionManual Assertion Based On ExperimentIMP:ARUK-UCL
Protein phosphorylationManual Assertion Based On ExperimentIDA:MGI
Regulation of axonogenesisManual Assertion Based On ExperimentIBA:GO_Central
Regulation of cytoskeleton organizationManual Assertion Based On ExperimentIMP:ARUK-UCL
Regulation of growthIEA:UniProtKB-KW
Regulation of MAPK cascadeManual Assertion Based On ExperimentIBA:GO_Central
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Stimulatory C-type lectin receptor signaling pathwayTAS:Reactome
Vascular endothelial growth factor receptor signaling pathwayTAS:Reactome

Cellular Location

Serine/threonine-protein kinase PAK 2
Cytoplasm
MYO18A mediates the cellular distribution of the PAK2-ARHGEF7-GIT1 complex to the inner surface of the cell membrane.
PAK-2p34
Nucleus
Cytoplasm, perinuclear region
Membrane
Interaction with ARHGAP10 probably changes PAK-2p34 location to cytoplasmic perinuclear region. Myristoylation changes PAK-2p34 location to the membrane.

PTM

Full-length PAK2 is autophosphorylated when activated by CDC42/p21. Following cleavage, both peptides, PAK-2p27 and PAK-2p34, become highly autophosphorylated, with PAK-2p27 being phosphorylated on serine and PAK-2p34 on threonine residues, respectively. Autophosphorylation of PAK-2p27 can occur in the absence of any effectors and is dependent on phosphorylation of Thr-402, because PAK-2p27 is acting as an exogenous substrate.
During apoptosis proteolytically cleaved by caspase-3 or caspase-3-like proteases to yield active PAK-2p34.
Ubiquitinated, leading to its proteasomal degradation.
PAK-2p34 is myristoylated.