P21-activated Kinases

P21-activated kinases (PAKs), EC 2.7.11.1, are serine/threonine kinases that are effector proteins for the Rho GTPases Cdc42 and Rac. Six PAK isoforms have been identified to date, which can be split into group I (PAK1, PAK2, PAK3) and group II (PAK4, PAK5, PAK6).

Products
Background
Literature
Gene Data

Inhibitors

Cat. No. Product Name / Activity
6177 AZ 13705339
Highly potent PAK1 and PAK2 inhibitor
5190 FRAX 486
Potent PAK inhibitor; brain penetrant and orally bioavailable
6029 FRAX 597
Potent group I PAK inhibitor
6051 G 5555
High affinity group I PAK inhibitor
6490 GNE 2861
Group II PAK inhibitor; potently inhibits PAK4 and PAK 6
3622 IPA 3
Group I PAK inhibitor
6132 NVS PAK1 1
Potent and selective PAK1 inhibitor
6005 PF 3758309 dihydrochloride
Potent PAK4 inhibitor; orally available

Other

Cat. No. Product Name / Activity
6133 NVS PAK1 C
Negative control of NVS PAK1 1 (Cat. No. 6132)
4212 PIR 3.5
Negative control of IPA 3 (Cat. No. 3622)

Related Targets

P21-activated kinases (PAKs), EC 2.7.11.1, are serine/threonine kinases that are effector proteins for the Rho GTPases Cdc42 and Rac. Six PAK isoforms have been identified to date, which can be split into two groups: group I - PAK1, PAK2 and PAK3; and group II - PAK4, PAK5 and PAK6. The PAK isoforms have varying levels of expression and tissue distribution, although they are all highly expressed in the nervous system.

Group A PAKs exist as homodimers in their inactive state, where their autoinhibitory domain (AID) overlaps with their GTPase binding domain (GBD). Binding of Cdc42 or Rac to the GBD, causes dissociation between the AID and dimerizing PAK, resulting in PAK monomers, which are autophosphorylated. In contrast group B PAKs are constitutively autophosphorylated, but the AID binds to the catalytic domain, maintaining PAK in an inactive conformation. Binding of Cdc42/Rac disrupts this interaction, resulting in PAK activation.

PAKs are physiologically involved in regulating the cytoskeleton, through controlling actin polymerization and therefore affecting cell shape, motility and adhesion. PAKs have a key role in neural development and morphology. Group A PAKs are involved in dendritic spine formation, while group B PAKs have a role in the formation of filopodia and neurite-like extensions in neurons. LIMK is a substrate of PAK; LIMK signaling inhibits actin depolymerization, which promotes the formation and stability of actin structures such as filopodia.

PAKs are also involved in the control of cell survival, proliferation and migration, with their abnormal expression being associated with many forms of cancer. Overexpression of PAK4 has been shown to be sufficient for oncogenesis, promoting anchorage-independent growth of fibroblasts, and increase migration and invasiveness, possibly through its activation of Aurora kinase A.

Furthermore PAK1 and PAK2 have been shown to be involved in cardiac ischemia and reperfusion injury, as well as promoting chemotaxis during inflammation.

External sources of pharmacological information for P21-activated Kinases :

Literature for P21-activated Kinases

Tocris offers the following scientific literature for P21-activated Kinases to showcase our products. We invite you to request* or download your copy today!

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PAK Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
PAK1 Human PAK1 NM_002576 Q13153
Mouse Pak1 NM_011035 O88643
Rat Pak1 NM_017198 P35465
PAK2 Human PAK2 NM_002577 Q13177
Mouse Pak2 NM_177326 Q8CIN4
Rat Pak2 NM_053306 Q64303
PAK3 Human PAK3 NM_002578 O75914
Mouse Pak3 NM_001195046 Q61036
Rat Pak3 NM_019210 Q62829
PAK4 Human PAK4 NM_001014831 O96013
Mouse Pak4 NM_027470 NP_081746
Rat Pak4 NM_001106238 NP_001099708
PAK5 (PAK7) Human PAK7 NM_020341 Q9P286
Mouse Pak7 NM_172858 Q8C015
Rat Pak7 NM_001107781 NP_001101251
PAK6 Human PAK6 NM_020168 Q9NQU5
Mouse Pak6 NM_001033254 Q3ULB5
Rat Pak6 NM_001106498 NP_001099968