>p21-Activated Kinase (PAK)
p21-Activated Kinase (PAK)
Sino Biological provides a comprehensive set of tools for p21-activated kinase (PAK) related studies, including proteins, antibodies (rabbit mAbs, mouse mAbs, and rabbit pAbs), ELISA kits, and ORF cDNA clones. The p21-activated kinases (PAKs) are established effectors of the small GTPases Rac1 and Cdc42. Although initially discovered as regulators of the actin cytoskeleton, they have subsequently been implicated in a wide range of biological activities, including cell morphology, motility, survival, gene transcription and hormone signalling. The mammalian p21-activated kinase family contains six serine/threonine kinases divided into two subgroups, group I (PAK 1-3) and group II (PAK4-6), based on their domain architecture and regulation.
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p21-Activated Kinase (PAK) Background
The p21-activated kinases (PAKs) are established effectors of the small GTPases Rac1 and Cdc42. Members of the Rho-family GTPases in the activated, GTP-bound state bind directly to p21-activated kinases (PAKs) through an amino-terminal p21 binding domain to affect kinase activation and signaling. Although initially discovered as regulators of the actin cytoskeleton, they have subsequently been implicated in a wide range of biological activities, including cell morphology, motility, survival, gene transcription and hormone signalling. The p21-activated kinases are members of the STE20 serine/threonine protein kinase family with two subgroups: PAK1, PAK2, and PAK3 (group A) and PAK4, PAK5, and PAK6 (group B), based on their domain architecture and regulation.
The p21-activated kinases (PAKs) functioning as dynamic signalling nodes present themselves as attractive therapeutic targets in tumours, neurological diseases and infection. PAKs have been shown to have major yet varied roles in oncogenic processes. Active p21-activated kinase 4 (PAK4) is required for Ras-driven NIH 3T3 cell transformation to facilitate anchorage-independent growth and affects profound cell morphological and cytoskeletal effects. Expression of activated PAK4 in NIH 3T3 cells is tumorigenic in nude mice, with tumors having less apoptosis (activated caspase 3 staining) and increased proliferation relative to control tumors. It has been demonstrated that p21-activated kinases (PAK1 and PAK3) and PAK activity are markedly reduced in cytosol from Alzheimer disease, accompanied by prominent cofilin pathology and downstream loss of the spine actin-regulatory protein Drebrin.
p21-Activated Kinase (PAK) Related Studies
- Cotteret S and Chernoff J (2002) The evolutionary history of effectors downstream of Cdc42 and Rac. Genome Biol 3, REVIEWS0002
- Eswaran J, et al. (2008) UnPAKing the class differences among p21-activated kinases. Trends Biochem Sci. 33(8):394-403.
- Ma QL, et al. (2008) p21-activated kinase-aberrant activation and translocation in Alzheimer disease pathogenesis. J Biol Chem. 283(20):14132-43.
- Szczepanowska J (2009) Involvement of Rac/Cdc42/PAK pathway in cytoskeletal rearrangements. Acta Biochim Pol 56, 225-234.
- Murray BW, et al. (2010) 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. 107(20):9446-51.