PAK1
Serine/threonine-protein kinase PAK 1 is an enzyme that in humans is encoded by the PAK1 gene.[1][2]
Function
PAK proteins are critical effectors that link the Rho_family_of_GTPases (Rho GTPases) to cytoskeleton reorganization and nuclear signaling. PAK proteins, a family of serine/threonine p21-activated kinases, include PAK1, PAK2, PAK3 and PAK4. These proteins serve as targets for the small GTP binding proteins Cdc42 and Rac and have been implicated in a wide range of biological activities. PAK1 regulates cell motility and morphology. Alternative transcripts of this gene have been found, but their full-length natures have not yet been determined.[3]
Interactions
PAK1 has been shown to interact with:
References
- ↑ Brown JL, Stowers L, Baer M, Trejo J, Coughlin S, Chant J (Mar 1997). "Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase pathway". Curr Biol 6 (5): 598–605. doi:10.1016/S0960-9822(02)00546-8. PMID 8805275.
- ↑ Bekri S, Adélaïde J, Merscher S, Grosgeorge J, Caroli-Bosc F, Perucca-Lostanlen D, Kelley PM, Pébusque MJ, Theillet C, Birnbaum D, Gaudray P (Apr 1998). "Detailed map of a region commonly amplified at 11q13-->q14 in human breast carcinoma". Cytogenet Cell Genet 79 (1–2): 125–31. doi:10.1159/000134699. PMID 9533029.
- ↑ "Entrez Gene: PAK1 p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast)".
- ↑ Zenke FT, Krendel M, DerMardirossian C, King CC, Bohl BP, Bokoch GM (Apr 2004). "p21-activated kinase 1 phosphorylates and regulates 14-3-3 binding to GEF-H1, a microtubule-localized Rho exchange factor". J. Biol. Chem. 279 (18): 18392–400. doi:10.1074/jbc.M400084200. PMID 14970201.
- ↑ Vadlamudi RK, Li F, Barnes CJ, Bagheri-Yarmand R, Kumar R (Feb 2004). "p41-Arc subunit of human Arp2/3 complex is a p21-activated kinase-1-interacting substrate". EMBO Rep. 5 (2): 154–60. doi:10.1038/sj.embor.7400079. PMC 1298990. PMID 14749719.
- ↑ Bagheri-Yarmand R, Mandal M, Taludker AH, Wang RA, Vadlamudi RK, Kung HJ, Kumar R (Aug 2001). "Etk/Bmx tyrosine kinase activates Pak1 and regulates tumorigenicity of breast cancer cells". J. Biol. Chem. 276 (31): 29403–9. doi:10.1074/jbc.M103129200. PMID 11382770.
- ↑ Zang M, Hayne C, Luo Z (Feb 2002). "Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1". J. Biol. Chem. 277 (6): 4395–405. doi:10.1074/jbc.M110000200. PMID 11733498.
- 1 2 Seoh ML, Ng CH, Yong J, Lim L, Leung T (Mar 2003). "ArhGAP15, a novel human RacGAP protein with GTPase binding property". FEBS Lett. 539 (1-3): 131–7. doi:10.1016/s0014-5793(03)00213-8. PMID 12650940.
- 1 2 Zhang B, Chernoff J, Zheng Y (Apr 1998). "Interaction of Rac1 with GTPase-activating proteins and putative effectors. A comparison with Cdc42 and RhoA". J. Biol. Chem. 273 (15): 8776–82. doi:10.1074/jbc.273.15.8776. PMID 9535855.
- ↑ Rashid T, Banerjee M, Nikolic M (Dec 2001). "Phosphorylation of Pak1 by the p35/Cdk5 kinase affects neuronal morphology". J. Biol. Chem. 276 (52): 49043–52. doi:10.1074/jbc.M105599200. PMID 11604394.
- ↑ Vadlamudi RK, Bagheri-Yarmand R, Yang Z, Balasenthil S, Nguyen D, Sahin AA, den Hollander P, Kumar R (Jun 2004). "Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes". Cancer Cell 5 (6): 575–85. doi:10.1016/j.ccr.2004.05.022. PMID 15193260.
- ↑ Edwards DC, Sanders LC, Bokoch GM, Gill GN (Sep 1999). "Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics". Nat. Cell Biol. 1 (5): 253–9. doi:10.1038/12963. PMID 10559936.
- ↑ Ku GM, Yablonski D, Manser E, Lim L, Weiss A (Feb 2001). "A PAK1-PIX-PKL complex is activated by the T-cell receptor independent of Nck, Slp-76 and LAT". EMBO J. 20 (3): 457–65. doi:10.1093/emboj/20.3.457. PMC 133476. PMID 11157752.
- ↑ Braverman LE, Quilliam LA (Feb 1999). "Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck". J. Biol. Chem. 274 (9): 5542–9. doi:10.1074/jbc.274.9.5542. PMID 10026169.
- ↑ Bokoch GM, Wang Y, Bohl BP, Sells MA, Quilliam LA, Knaus UG (Oct 1996). "Interaction of the Nck adapter protein with p21-activated kinase (PAK1)". J. Biol. Chem. 271 (42): 25746–9. doi:10.1074/jbc.271.42.25746. PMID 8824201.
- ↑ Xia C, Ma W, Stafford LJ, Marcus S, Xiong WC, Liu M (May 2001). "Regulation of the p21-activated kinase (PAK) by a human Gbeta -like WD-repeat protein, hPIP1". Proc. Natl. Acad. Sci. U.S.A. 98 (11): 6174–9. doi:10.1073/pnas.101137298. PMC 33441. PMID 11371639.
- ↑ Katoh H, Negishi M (Jul 2003). "RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo". Nature 424 (6947): 461–4. doi:10.1038/nature01817. PMID 12879077.
- ↑ Wang, J; Wu, JW; Wang, ZX (7 December 2011). "Structural insights into the autoactivation mechanism of p21-activated protein kinase.". Structure (London, England : 1993) 19 (12): 1752–61. doi:10.1016/j.str.2011.10.013. PMID 22153498.
- ↑ Xu, Q.; Malecka, K. L.; Fink, L.; Jordan, E. J.; Duffy, E.; Kolander, S.; Peterson, J. R.; Dunbrack, R. L. (1 December 2015). "Identifying three-dimensional structures of autophosphorylation complexes in crystals of protein kinases". Science Signaling 8 (405): rs13. doi:10.1126/scisignal.aaa6711.
Further reading
- Trono D, Wang JK (1997). "Nef and PAK: virulence factor and cellular accomplice". Chem. Biol. 4 (1): 13–5. doi:10.1016/S1074-5521(97)90232-5. PMID 9070423.
- Bagrodia S, Cerione RA (1999). "Pak to the future". Trends Cell Biol. 9 (9): 350–5. doi:10.1016/S0962-8924(99)01618-9. PMID 10461188.
- Geyer M, Fackler OT, Peterlin BM (2001). "Structure–function relationships in HIV-1 Nef". EMBO Rep. 2 (7): 580–5. doi:10.1093/embo-reports/kve141. PMC 1083955. PMID 11463741.
- Jaffer ZM, Chernoff J (2002). "p21-activated kinases: three more join the Pak". Int. J. Biochem. Cell Biol. 34 (7): 713–7. doi:10.1016/S1357-2725(01)00158-3. PMID 11950587.
- Greenway AL, Holloway G, McPhee DA, Ellis P, Cornall A, Lidman M (2004). "HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication". J. Biosci. 28 (3): 323–35. doi:10.1007/BF02970151. PMID 12734410.
- Joseph AM, Kumar M, Mitra D (2005). "Nef: "necessary and enforcing factor" in HIV infection". Curr. HIV Res. 3 (1): 87–94. doi:10.2174/1570162052773013. PMID 15638726.
- Anderson JL, Hope TJ (2005). "HIV accessory proteins and surviving the host cell". Current HIV/AIDS reports 1 (1): 47–53. doi:10.1007/s11904-004-0007-x. PMID 16091223.
- Sheehan KA, Ke Y, Solaro RJ (2007). "p21-Activated kinase-1 and its role in integrated regulation of cardiac contractility". Am. J. Physiol. Regul. Integr. Comp. Physiol. 293 (3): R963–73. doi:10.1152/ajpregu.00253.2007. PMID 17609315.
- Martin GA, Bollag G, McCormick F, Abo A (1995). "A novel serine kinase activated by rac1/CDC42Hs-dependent autophosphorylation is related to PAK65 and STE20". EMBO J. 14 (9): 1970–8. PMC 398296. PMID 7744004.
- Sawai ET, Baur AS, Peterlin BM, Levy JA, Cheng-Mayer C (1995). "A conserved domain and membrane targeting of Nef from HIV and SIV are required for association with a cellular serine kinase activity". J. Biol. Chem. 270 (25): 15307–14. doi:10.1074/jbc.270.25.15307. PMID 7797518.
- Manser E, Leung T, Salihuddin H, Zhao ZS, Lim L (1994). "A brain serine/threonine protein kinase activated by Cdc42 and Rac1". Nature 367 (6458): 40–6. doi:10.1038/367040a0. PMID 8107774.
- Sawai ET, Baur A, Struble H, Peterlin BM, Levy JA, Cheng-Mayer C (1994). "Human immunodeficiency virus type 1 Nef associates with a cellular serine kinase in T lymphocytes". Proc. Natl. Acad. Sci. U.S.A. 91 (4): 1539–43. doi:10.1073/pnas.91.4.1539. PMC 43195. PMID 8108442.
- Nunn MF, Marsh JW (1996). "Human immunodeficiency virus type 1 Nef associates with a member of the p21-activated kinase family". J. Virol. 70 (9): 6157–61. PMC 190639. PMID 8709241.
- Luo T, Garcia JV (1996). "The association of Nef with a cellular serine/threonine kinase and its enhancement of infectivity are viral isolate dependent". J. Virol. 70 (9): 6493–6. PMC 190686. PMID 8709288.
- Bokoch GM, Wang Y, Bohl BP, Sells MA, Quilliam LA, Knaus UG (1996). "Interaction of the Nck adapter protein with p21-activated kinase (PAK1)". J. Biol. Chem. 271 (42): 25746–9. doi:10.1074/jbc.271.42.25746. PMID 8824201.
- Wiskerchen M, Cheng-Mayer C (1996). "HIV-1 Nef association with cellular serine kinase correlates with enhanced virion infectivity and efficient proviral DNA synthesis". Virology 224 (1): 292–301. doi:10.1006/viro.1996.0531. PMID 8862424.
- Sawai ET, Khan IH, Montbriand PM, Peterlin BM, Cheng-Mayer C, Luciw PA (1997). "Activation of PAK by HIV and SIV Nef: importance for AIDS in rhesus macaques". Curr. Biol. 6 (11): 1519–27. doi:10.1016/S0960-9822(96)00757-9. PMID 8939608.
- Manser E, Huang HY, Loo TH, Chen XQ, Dong JM, Leung T, Lim L (1997). "Expression of constitutively active alpha-PAK reveals effects of the kinase on actin and focal complexes". Mol. Cell. Biol. 17 (3): 1129–43. PMC 231838. PMID 9032240.
External links
- PAK1 Info with links in the Cell Migration Gateway
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