Protein: Serine/threonine-protein kinase PAK 2 (EC 2.7.11.1) (Gamma-PAK) (PAK65) (S6/H4 kinase) (p21-activated kinase 2) (PAK-2) (p58) [Cleaved into: PAK-2p27 (p27); PAK-2p34 (p34) (C-t-PAK2)] (Q13177)
Organism: Homo sapiens (Human)
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. Phosphorylates CASP7, thereby preventing its activity. 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.
Subcellular location: [Serine/threonine-protein kinase PAK 2]: Cytoplasm {ECO:0000269|PubMed:19923322, ECO:0000269|PubMed:21555521}. Nucleus {ECO:0000269|PubMed:12853446, ECO:0000269|PubMed:21555521}. Note=MYO18A mediates the cellular distribution of the PAK2-ARHGEF7-GIT1 complex to the inner surface of the cell membrane. {ECO:0000269|PubMed:19923322}.; SUBCELLULAR LOCATION: [PAK-2p34]: Nucleus {ECO:0000269|PubMed:12853446}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:15471851}. Membrane {ECO:0000269|PubMed:16617111}; Lipid-anchor {ECO:0000269|PubMed:16617111}. Note=Interaction with ARHGAP10 probably changes PAK-2p34 location to cytoplasmic perinuclear region (PubMed:15471851). Myristoylation changes PAK-2p34 location to the membrane (PubMed:16617111). {ECO:0000269|PubMed:15471851, ECO:0000269|PubMed:16617111}.
Interaction partners:
- Rho guanine nucleotide exchange factor 7
- Cell division control protein 42 homolog
- Rho guanine nucleotide exchange factor 6
- Ras-related C3 botulinum toxin substrate 2
- Rho GTPase-activating protein 10
- Ras-related C3 botulinum toxin substrate 1
- Cytoplasmic protein NCK2
- SH2/SH3 adapter protein NCK1
- RAF proto-oncogene serine/threonine-protein kinase
- Caspase-3
Sequence:
MSDNGELEDKPPAPPVRMSSTIFSTGGKDPLSANHSLKPLPSVPEEKKPRHKIISIFSGTEKGSKKKEKERPEISPPSDFEHTIHVGFDAVTGEFTGMPEQWARLLQTSNITKLEQKKNPQAVLDVLKFYDSNTVKQKYLSFTPPEKDGFPSGTPALNAKGTEAPAVVTEEEDDDEETAPPVIAPRPDHTKSIYTRSVIDPVPAPVGDSHVDGAAKSLDKQKKKTKMTDEEIMEKLRTIVSIGDPKKKYTRYEKIGQGASGTVFTATDVALGQEVAIKQINLQKQPKKELIINEILVMKELKNPNIVNFLDSYLVGDELFVVMEYLAGGSLTDVVTETCMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMEGSVKLTDFGFCAQITPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIATNGTPELQNPEKLSPIFRDFLNRCLEMDVEKRGSAKELLQHPFLKLAKPLSSLTPLIMAAKEAMKSNR