PAK1

P21 protein (Cdc42/Rac)-activated kinase 1
PDB rendering based on 1e0a.
Available structures PDB 1F3M, 1YHV, 1YHW, 1ZSG, 2HY8, 2QME, 3DVP, 3FXZ, 3FY0
Identifiers
Symbols	PAK1; MGC130000; MGC130001; PAKalpha
External IDs	OMIM: 602590 MGI: 1339975 HomoloGene: 1936 GeneCards: PAK1 Gene
EC number	2.7.11.1
Gene Ontology Molecular function • nucleotide binding • protein kinase activity • protein serine/threonine kinase activity • protein serine/threonine kinase activity • protein serine/threonine kinase activity • protein binding • protein binding • collagen binding • ATP binding Cellular component • cytoplasm • Golgi apparatus • cytosol • cytosol • plasma membrane • focal adhesion • cell junction Biological process • MAPKKK cascade • protein phosphorylation • apoptosis • ER-nucleus signaling pathway • cytoskeleton organization • axon guidance • T cell costimulation • positive regulation of peptidyl-serine phosphorylation • positive regulation of JUN kinase activity • protein autophosphorylation • T cell receptor signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5058	18479
Ensembl	ENSG00000149269	ENSMUSG00000030774
UniProt	Q13153	Q9R2B2
RefSeq (mRNA)	NM_001128620.1	NM_011035.2
RefSeq (protein)	NP_001122092.1	NP_035165.2
Location (UCSC)	Chr 11: 77.03 – 77.19 Mb	Chr 7: 104.94 – 105.06 Mb
PubMed search	[1]	[2]

Serine/threonine-protein kinase PAK 1 is an enzyme that in humans is encoded by the PAK1 gene.^[1][2]

PAK proteins are critical effectors that link RhoGTPases 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 C-Raf,^[4] NCK1,^[5][6][7] LIMK1,^[8] RAC1,^[9][10][11] ARHGEF2,^[12] BMX,^[13] ARPC1B,^[14] DYNLL1,^[15] Cyclin-dependent kinase 5,^[16] PAK1IP1^[17] and CDC42.^[10][11]

References

1. ^ 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. 
2. ^ Bekri S, Adelaide J, Merscher S, Grosgeorge J, Caroli-Bosc F, Perucca-Lostanlen D, Kelley PM, Pebusque 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. 
3. ^ "Entrez Gene: PAK1 p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5058. 
4. ^ Zang, Mengwei; Hayne Cynthia, Luo Zhijun (Feb. 2002). "Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1". J. Biol. Chem. (United States) 277 (6): 4395–405. doi:10.1074/jbc.M110000200. ISSN 0021-9258. PMID 11733498. 
5. ^ Ku, G M; 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. (England) 20 (3): 457–65. doi:10.1093/emboj/20.3.457. ISSN 0261-4189. PMC 133476. PMID 11157752. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=133476. 
6. ^ Braverman, L E; Quilliam L A (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. (UNITED STATES) 274 (9): 5542–9. doi:10.1074/jbc.274.9.5542. ISSN 0021-9258. PMID 10026169. 
7. ^ Bokoch, G M; Wang Y, Bohl B P, Sells M A, Quilliam L A, Knaus U G (Oct. 1996). "Interaction of the Nck adapter protein with p21-activated kinase (PAK1)". J. Biol. Chem. (UNITED STATES) 271 (42): 25746–9. doi:10.1074/jbc.271.42.25746. ISSN 0021-9258. PMID 8824201. 
8. ^ Edwards, D C; Sanders L C, Bokoch G M, Gill G N (Sep. 1999). "Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics". Nat. Cell Biol. (ENGLAND) 1 (5): 253–9. doi:10.1038/12963. ISSN 1465-7392. PMID 10559936. 
9. ^ Katoh, Hironori; Negishi Manabu (Jul. 2003). "RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo". Nature (England) 424 (6947): 461–4. doi:10.1038/nature01817. PMID 12879077. 
10. ^ ^{a b} Seoh, Mui Leng; Ng Chong Han, Yong Jeffery, Lim Louis, Leung Thomas (Mar. 2003). "ArhGAP15, a novel human RacGAP protein with GTPase binding property". FEBS Lett. (Netherlands) 539 (1–3): 131–7. doi:10.1016/S0014-5793(03)00213-8. ISSN 0014-5793. PMID 12650940. 
11. ^ ^{a b} 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. (UNITED STATES) 273 (15): 8776–82. doi:10.1074/jbc.273.15.8776. ISSN 0021-9258. PMID 9535855. 
12. ^ Zenke, Frank T; Krendel Mira, DerMardirossian Celine, King Charles C, Bohl Benjamin P, Bokoch Gary M (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. (United States) 279 (18): 18392–400. doi:10.1074/jbc.M400084200. ISSN 0021-9258. PMID 14970201. 
13. ^ Bagheri-Yarmand, R; Mandal M, Taludker A H, Wang R A, Vadlamudi R K, Kung H J, Kumar R (Aug. 2001). "Etk/Bmx tyrosine kinase activates Pak1 and regulates tumorigenicity of breast cancer cells". J. Biol. Chem. (United States) 276 (31): 29403–9. doi:10.1074/jbc.M103129200. ISSN 0021-9258. PMID 11382770. 
14. ^ Vadlamudi, Ratna K; Li Feng, Barnes Christopher J, Bagheri-Yarmand Rozita, Kumar Rakesh (Feb. 2004). "p41-Arc subunit of human Arp2/3 complex is a p21-activated kinase-1-interacting substrate". EMBO Rep. (England) 5 (2): 154–60. doi:10.1038/sj.embor.7400079. ISSN 1469-221X. PMC 1298990. PMID 14749719. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1298990. 
15. ^ Vadlamudi, Ratna K; Bagheri-Yarmand Rozita, Yang Zhibo, Balasenthil Seetharaman, Nguyen Diep, Sahin Aysegul A, den Hollander Petra, Kumar Rakesh (Jun. 2004). "Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes". Cancer Cell (United States) 5 (6): 575–85. doi:10.1016/j.ccr.2004.05.022. ISSN 1535-6108. PMID 15193260. 
16. ^ Rashid, T; Banerjee M, Nikolic M (Dec. 2001). "Phosphorylation of Pak1 by the p35/Cdk5 kinase affects neuronal morphology". J. Biol. Chem. (United States) 276 (52): 49043–52. doi:10.1074/jbc.M105599200. ISSN 0021-9258. PMID 11604394. 
17. ^ Xia, C; Ma W, Stafford L J, Marcus S, Xiong W C, Liu M (May. 2001). "Regulation of the p21-activated kinase (PAK) by a human Gβ-like WD-repeat protein, hPIP1". Proc. Natl. Acad. Sci. U.S.A. (United States) 98 (11): 6174–9. doi:10.1073/pnas.101137298. ISSN 0027-8424. PMC 33441. PMID 11371639. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=33441. 

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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1083955. 
• 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 et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=398296. 
• Sawai ET, Baur AS, Peterlin BM et al. (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 et al. (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 et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=43195. 
• 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=190639. 
• 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=190686. 
• Bokoch GM, Wang Y, Bohl BP et al. (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 et al. (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 et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=231838. 

External links

• PAK1 Info with links in the Cell Migration Gateway