Target General Infomation
Target ID
T98293 (Former ID: TTDI02145)
Target Name
PAK-4 protein kinase (PAK4)
p21-activated kinase 4; Serine/threonine-protein kinase PAK 4; PAK-4; KIAA1142
Gene Name
Target Type
Clinical trial target
Disease [+] 2 Target-related Diseases +
1 Malignant haematopoietic neoplasm [ICD-11: 2B33]
2 Solid tumour/cancer [ICD-11: 2A00-2F9Z]
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.
BioChemical Class
UniProt ID
EC Number
Drugs and Modes of Action
Clinical Trial Drug(s) [+] 2 Clinical Trial Drugs +
1 KPT-9274 Drug Info Phase 1 Non-hodgkin lymphoma [2]
2 PF-3758309 Drug Info Phase 1 Solid tumour/cancer [1]
Mode of Action [+] 1 Modes of Action +
Inhibitor [+] 2 Inhibitor drugs +
1 KPT-9274 Drug Info [2]
2 PF-3758309 Drug Info [1]
Target Regulators
Target-regulating microRNAs
Target-interacting Proteins
Target Affiliated Biological Pathways
KEGG Pathway [+] 8 KEGG Pathways +
1 ErbB signaling pathway
2 Ras signaling pathway
3 Axon guidance
4 Focal adhesion
5 T cell receptor signaling pathway
6 Regulation of actin cytoskeleton
7 MicroRNAs in cancer
8 Renal cell carcinoma
Panther Pathway [+] 2 Panther Pathways +
1 Cytoskeletal regulation by Rho GTPase
2 Inflammation mediated by chemokine and cytokine signaling pathway
PID Pathway [+] 3 PID Pathways +
1 Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
2 CDC42 signaling events
3 FGF signaling pathway
WikiPathways [+] 4 WikiPathways +
1 ErbB Signaling Pathway
2 Regulation of Actin Cytoskeleton
3 Focal Adhesion
4 Integrin-mediated Cell Adhesion
REF 1 Small-molecule p21-activated kinase inhibitor PF-3758309 is a potent inhibitor of oncogenic signaling and tumor growth. Proc Natl Acad Sci U S A. 2010 May 18;107(20):9446-51.
REF 2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

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