PAK2

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 (PubMed:12853446, PubMed:16617111, PubMed:19273597, PubMed:19923322, PubMed:33693784, PubMed:7744004, PubMed:9171063). Acts as a downstream effector of the small GTPases CDC42 and RAC1 (PubMed:7744004). 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 (PubMed:7744004). Full-length PAK2 stimulates cell survival and cell growth (PubMed:7744004). Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration (PubMed:21317288). Phosphorylates JUN and plays an important role in EGF-induced cell proliferation (PubMed:21177766). Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP (PubMed:21724829). Phosphorylates CASP7, thereby preventing its activity (PubMed:21555521, PubMed:27889207). Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis (PubMed:19273597, PubMed:19923322). 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 (PubMed:12853446, PubMed:16617111, PubMed:9171063). Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation (PubMed:15234964).

Involvement in disease

Knobloch syndrome 2

KNO2

An autosomal dominant form of Knobloch syndrome characterized by high myopia, vitreoretinal degeneration, retinal detachment, occipital encephalocele or scalp lesions, and mild to severe psychomotor delay.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

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

PAK-2p34 is myristoylated.

Sequence Similarities

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.

Tissue Specificity

Ubiquitously expressed. Higher levels seen in skeletal muscle, ovary, thymus and spleen.

Cellular localization

• Serine/threonine-protein kinase PAK 2
• Cytoplasm
• Nucleus
• 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
• Lipid-anchor
• Interaction with ARHGAP10 probably changes PAK-2p34 location to cytoplasmic perinuclear region (PubMed:15471851). Myristoylation changes PAK-2p34 location to the membrane (PubMed:16617111).

Alternative names

Serine/threonine-protein kinase PAK 2, Gamma-PAK, PAK65, S6/H4 kinase, p21-activated kinase 2, p58, PAK-2, PAK2

Database links

swissprot:Q13177 entrezGene:5062 omim:300142 omim:605022 omim:602590 genbank:NP_002568.2 swissprot:O75914 swissprot:Q13153 entrezGene:5058 entrezGene:5063

Other research areas

• Epigenetics