TARGETID

T98293

FORMERID

TTDI02145

UNIPROID

PAK4_HUMAN

TARGNAME

PAK-4 protein kinase (PAK4)

GENENAME

PAK4

TARGTYPE

Clinical trial target

SYNONYMS

p21-activated kinase 4; Serine/threonine-protein kinase PAK 4; PAK-4; KIAA1142

FUNCTION

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. 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.

PDBSTRUC

5ZJW; 5XVG; 5XVF; 5XVA; 5VEF

BIOCLASS

Kinase

ECNUMBER

EC 2.7.11.1

SEQUENCE

MFGKRKKRVEISAPSNFEHRVHTGFDQHEQKFTGLPRQWQSLIEESARRPKPLVDPACITSIQPGAPKTIVRGSKGAKDGALTLLLDEFENMSVTRSNSLRRDSPPPPARARQENGMPEEPATTARGGPGKAGSRGRFAGHSEAGGGSGDRRRAGPEKRPKSSREGSGGPQESSRDKRPLSGPDVGTPQPAGLASGAKLAAGRPFNTYPRADTDHPSRGAQGEPHDVAPNGPSAGGLAIPQSSSSSSRPPTRARGAPSPGVLGPHASEPQLAPPACTPAAPAVPGPPGPRSPQREPQRVSHEQFRAALQLVVDPGDPRSYLDNFIKIGEGSTGIVCIATVRSSGKLVAVKKMDLRKQQRRELLFNEVVIMRDYQHENVVEMYNSYLVGDELWVVMEFLEGGALTDIVTHTRMNEEQIAAVCLAVLQALSVLHAQGVIHRDIKSDSILLTHDGRVKLSDFGFCAQVSKEVPRRKSLVGTPYWMAPELISRLPYGPEVDIWSLGIMVIEMVDGEPPYFNEPPLKAMKMIRDNLPPRLKNLHKVSPSLKGFLDRLLVRDPAQRATAAELLKHPFLAKAGPPASIVPLMRQNRTR

DRUGINFO

KPT-9274

DRUGINFO

PF-3758309

KEGGPATH

hsa04012:ErbB signaling pathway

KEGGPATH

hsa04014:Ras signaling pathway

KEGGPATH

hsa04360:Axon guidance

KEGGPATH

hsa04510:Focal adhesion

KEGGPATH

hsa04660:T cell receptor signaling pathway

KEGGPATH

hsa04810:Regulation of actin cytoskeleton