PAK4
Serine/threonine-protein kinase PAK 4 is an enzyme that in humans is encoded by the PAK4 gene.[1][2][3]
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.[3]
Interactions
PAK4 has been shown to interact with CDC42,[4][5][1] Integrin, beta 5[6] and LIMK1.[7]
References
- ^ a b Abo A, Qu J, Cammarano MS, Dan C, Fritsch A, Baud V, Belisle B, Minden A (Jan 1999). "PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia". EMBO J 17 (22): 6527–40. doi:10.1093/emboj/17.22.6527. PMC 1171000. PMID 9822598. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1171000.
- ^ Bagrodia S, Cerione RA (Oct 1999). "Pak to the future". Trends Cell Biol 9 (9): 350–5. doi:10.1016/S0962-8924(99)01618-9. PMID 10461188.
- ^ a b "Entrez Gene: PAK4 p21(CDKN1A)-activated kinase 4". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10298.
- ^ Ewing, Rob M; Chu Peter, Elisma Fred, Li Hongyan, Taylor Paul, Climie Shane, McBroom-Cerajewski Linda, Robinson Mark D, O'Connor Liam, Li Michael, Taylor Rod, Dharsee Moyez, Ho Yuen, Heilbut Adrian, Moore Lynda, Zhang Shudong, Ornatsky Olga, Bukhman Yury V, Ethier Martin, Sheng Yinglun, Vasilescu Julian, Abu-Farha Mohamed, Lambert Jean-Philippe, Duewel Henry S, Stewart Ian I, Kuehl Bonnie, Hogue Kelly, Colwill Karen, Gladwish Katharine, Muskat Brenda, Kinach Robert, Adams Sally-Lin, Moran Michael F, Morin Gregg B, Topaloglou Thodoros, Figeys Daniel (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. (England) 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1847948.
- ^ Dan, Chuntao; Nath Niharika, Liberto Muriel, Minden Audrey (Jan. 2002). "PAK5, a new brain-specific kinase, promotes neurite outgrowth in N1E-115 cells". Mol. Cell. Biol. (United States) 22 (2): 567–77. doi:10.1128/MCB.22.2.567-577.2002. ISSN 0270-7306. PMC 139731. PMID 11756552. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139731.
- ^ Zhang, Hongquan; Li Zhilun, Viklund Eva-Karin, Strömblad Staffan (Sep. 2002). "P21-activated kinase 4 interacts with integrin alpha v beta 5 and regulates alpha v beta 5-mediated cell migration". J. Cell Biol. (United States) 158 (7): 1287–97. doi:10.1083/jcb.200207008. ISSN 0021-9525. PMC 2173231. PMID 12356872. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2173231.
- ^ Dan, C; Kelly A, Bernard O, Minden A (Aug. 2001). "Cytoskeletal changes regulated by the PAK4 serine/threonine kinase are mediated by LIM kinase 1 and cofilin". J. Biol. Chem. (United States) 276 (34): 32115–21. doi:10.1074/jbc.M100871200. ISSN 0021-9258. PMID 11413130.
Further reading
- Wells CM, Abo A, Ridley AJ (2002). "PAK4 is activated via PI3K in HGF-stimulated epithelial cells". J. Cell Sci. 115 (Pt 20): 3947–56. doi:10.1242/jcs.00080. PMID 12244132.
- Hirosawa M, Nagase T, Ishikawa K, et al. (2000). "Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain". DNA Res. 6 (5): 329–36. doi:10.1093/dnares/6.5.329. PMID 10574461.
- Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310948.
- Dan C, Kelly A, Bernard O, Minden A (2001). "Cytoskeletal changes regulated by the PAK4 serine/threonine kinase are mediated by LIM kinase 1 and cofilin". J. Biol. Chem. 276 (34): 32115–21. doi:10.1074/jbc.M100871200. PMID 11413130.
- Zhang H, Li Z, Viklund EK, Strömblad S (2002). "P21-activated kinase 4 interacts with integrin alpha v beta 5 and regulates alpha v beta 5-mediated cell migration". J. Cell Biol. 158 (7): 1287–97. doi:10.1083/jcb.200207008. PMC 2173231. PMID 12356872. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2173231.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Lu Y, Pan ZZ, Devaux Y, Ray P (2003). "p21-activated protein kinase 4 (PAK4) interacts with the keratinocyte growth factor receptor and participates in keratinocyte growth factor-mediated inhibition of oxidant-induced cell death". J. Biol. Chem. 278 (12): 10374–80. doi:10.1074/jbc.M205875200. PMID 12529371.
- Barac A, Basile J, Vázquez-Prado J, et al. (2004). "Direct interaction of p21-activated kinase 4 with PDZ-RhoGEF, a G protein-linked Rho guanine exchange factor". J. Biol. Chem. 279 (7): 6182–9. doi:10.1074/jbc.M309579200. PMID 14625312.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Jin J, Smith FD, Stark C, et al. (2004). "Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization". Curr. Biol. 14 (16): 1436–50. doi:10.1016/j.cub.2004.07.051. PMID 15324660.
- Ballif BA, Villén J, Beausoleil SA, et al. (2005). "Phosphoproteomic analysis of the developing mouse brain". Mol. Cell Proteomics 3 (11): 1093–101. doi:10.1074/mcp.M400085-MCP200. PMID 15345747.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928.
- Wiemann S, Arlt D, Huber W, et al. (2004). "From ORFeome to biology: a functional genomics pipeline". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528930.
- Soosairajah J, Maiti S, Wiggan O, et al. (2005). "Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin". EMBO J. 24 (3): 473–86. doi:10.1038/sj.emboj.7600543. PMC 548651. PMID 15660133. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=548651.
- Benzinger A, Muster N, Koch HB, et al. (2005). "Targeted proteomic analysis of 14-3-3 sigma, a p53 effector commonly silenced in cancer". Mol. Cell Proteomics 4 (6): 785–95. doi:10.1074/mcp.M500021-MCP200. PMID 15778465.
- Callow MG, Zozulya S, Gishizky ML, et al. (2005). "PAK4 mediates morphological changes through the regulation of GEF-H1". J. Cell. Sci. 118 (Pt 9): 1861–72. doi:10.1242/jcs.02313. PMID 15827085.
- Stelzl U, Worm U, Lalowski M, et al. (2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. PMID 16169070.
- Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
External links
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PDB gallery
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2bva: CRYSTAL STRUCTURE OF THE HUMAN P21-ACTIVATED KINASE 4
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2cdz: CRYSTAL STRUCTURE OF THE HUMAN P21-ACTIVATED KINASE 4 IN COMPLEX WITH CGP74514A
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2j0i: CRYSTAL STRUCTURE OF THE HUMAN P21-ACTIVATED KINASE 4
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2ov2: The crystal structure of the human RAC3 in complex with the CRIB domain of human p21-activated kinase 4 (PAK4)
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