PAK4

PAK proteins, a family of serine/threonine p21-activating kinases, include PAK1, PAK2, PAK3 and PAK4. PAK proteins are critical effectors that link Rho GTPases to cytoskeleton reorganization and nuclear signaling. They serve as targets for the small GTP binding proteins Cdc42 and Rac and have been implicated in a wide range of biological activities. PAK4 interacts specifically with the GTP-bound form of Cdc42Hs and weakly activates the JNK family of MAP kinases. PAK4 is a mediator of filopodia formation and may play a role in the reorganization of the actin cytoskeleton. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq]

p21 protein (Cdc42/Rac)-activated kinase 4

Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, growth, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN.

Apoptotic processManual Assertion Based On ExperimentTAS:UniProtKB
Cell cycleIEA:UniProtKB-KW
Cell migrationManual Assertion Based On ExperimentTAS:UniProtKB
Cellular response to organic cyclic compoundIEA:Ensembl
Cytoskeleton organizationManual Assertion Based On ExperimentTAS:UniProtKB
Dendritic spine developmentIEA:Ensembl
Intracellular signal transductionManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of endothelial cell apoptotic processManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of angiogenesisManual Assertion Based On ExperimentIMP:BHF-UCL
Protein phosphorylationManual Assertion Based On ExperimentIBA:GO_Central
Regulation of cell growthManual Assertion Based On ExperimentTAS:UniProtKB
Regulation of MAPK cascadeManual Assertion Based On ExperimentIBA:GO_Central
Signal transductionManual Assertion Based On ExperimentTAS:UniProtKB

Cytoplasm
Seems to shuttle between cytoplasmic compartments depending on the activating effector. For example, can be found on the cell periphery after activation of growth-factor or integrin-mediated signaling pathways.

Autophosphorylated on serine residues when activated by CDC42/p21 (Ref.32). Phosphorylated on tyrosine residues upon stimulation of FGFR2 (By similarity).
Methylated by SETD6.
Polyubiquitinated, leading to its proteasomal degradation.