MAPK14

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Mitogen-activated protein kinase 14
Protein MAPK14 PDB 1a9u.png
PDB rendering based on 1a9u.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols MAPK14 ; CSBP; CSBP1; CSBP2; CSPB1; EXIP; Mxi2; PRKM14; PRKM15; RK; SAPK2A; p38; p38ALPHA
External IDs OMIM600289 MGI1346865 HomoloGene31777 ChEMBL: 260 GeneCards: MAPK14 Gene
EC number 2.7.11.24
RNA expression pattern
PBB GE MAPK14 202530 at tn.png
PBB GE MAPK14 210449 x at tn.png
PBB GE MAPK14 211087 x at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1432 26416
Ensembl ENSG00000112062 ENSMUSG00000053436
UniProt Q16539 P47811
RefSeq (mRNA) NM_001315 NM_001168508
RefSeq (protein) NP_001306 NP_001161980
Location (UCSC) Chr 6:
36 – 36.08 Mb
Chr 17:
28.69 – 28.75 Mb
PubMed search [1] [2]

Mitogen-activated protein kinase 14, also called p38-α, is an enzyme that in humans is encoded by the MAPK14 gene.[1]

Function[edit]

The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various environmental stresses and proinflammatory cytokines. The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K7IP1/TAB1 protein with this kinase. The substrates of this kinase include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of this kinase in stress-related transcription and cell cycle regulation, as well as in genotoxic stress response. Four alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported.[2]

Interactions[edit]

MAPK14 has been shown to interact with:

References[edit]

  1. ^ Lee JC, Laydon JT, McDonnell PC, Gallagher TF, Kumar S, Green D et al. (January 1995). "A protein kinase involved in the regulation of inflammatory cytokine biosynthesis". Nature 372 (6508): 739–46. doi:10.1038/372739a0. PMID 7997261. 
  2. ^ "Entrez Gene: MAPK14 mitogen-activated protein kinase 14". 
  3. ^ a b Rane MJ, Coxon PY, Powell DW, Webster R, Klein JB, Pierce W et al. (February 2001). "p38 Kinase-dependent MAPKAPK-2 activation functions as 3-phosphoinositide-dependent kinase-2 for Akt in human neutrophils". J. Biol. Chem. 276 (5): 3517–23. doi:10.1074/jbc.M005953200. PMID 11042204. 
  4. ^ Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ et al. (March 1995). "Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine". J. Biol. Chem. 270 (13): 7420–6. PMID 7535770. 
  5. ^ a b Chen Z, Cobb MH (May 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol. Chem. 276 (19): 16070–5. doi:10.1074/jbc.M100681200. PMID 11279118. 
  6. ^ Tournier C, Whitmarsh AJ, Cavanagh J, Barrett T, Davis RJ (July 1997). "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S.A. 94 (14): 7337–42. PMC 23822. PMID 9207092. 
  7. ^ a b Bulavin DV, Higashimoto Y, Popoff IJ, Gaarde WA, Basrur V, Potapova O et al. (May 2001). "Initiation of a G2/M checkpoint after ultraviolet radiation requires p38 kinase". Nature 411 (6833): 102–7. doi:10.1038/35075107. PMID 11333986. 
  8. ^ Sayed M, Kim SO, Salh BS, Issinger OG, Pelech SL (June 2000). "Stress-induced activation of protein kinase CK2 by direct interaction with p38 mitogen-activated protein kinase". J. Biol. Chem. 275 (22): 16569–73. doi:10.1074/jbc.M000312200. PMID 10747897. 
  9. ^ a b c Tanoue T, Yamamoto T, Maeda R, Nishida E (July 2001). "A Novel MAPK phosphatase MKP-7 acts preferentially on JNK/SAPK and p38 alpha and beta MAPKs". J. Biol. Chem. 276 (28): 26629–39. doi:10.1074/jbc.M101981200. PMID 11359773. 
  10. ^ a b c Tanoue T, Maeda R, Adachi M, Nishida E (February 2001). "Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions". EMBO J. 20 (3): 466–79. doi:10.1093/emboj/20.3.466. PMC 133461. PMID 11157753. 
  11. ^ Tanoue T, Moriguchi T, Nishida E (July 1999). "Molecular cloning and characterization of a novel dual specificity phosphatase, MKP-5". J. Biol. Chem. 274 (28): 19949–56. PMID 10391943. 
  12. ^ Masuda K, Shima H, Watanabe M, Kikuchi K (October 2001). "MKP-7, a novel mitogen-activated protein kinase phosphatase, functions as a shuttle protein". J. Biol. Chem. 276 (42): 39002–11. doi:10.1074/jbc.M104600200. PMID 11489891. 
  13. ^ Slack DN, Seternes OM, Gabrielsen M, Keyse SM (May 2001). "Distinct binding determinants for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase phosphatase-1". J. Biol. Chem. 276 (19): 16491–500. doi:10.1074/jbc.M010966200. PMID 11278799. 
  14. ^ Kim MJ, Park BJ, Kang YS, Kim HJ, Park JH, Kang JW et al. (July 2003). "Downregulation of FUSE-binding protein and c-myc by tRNA synthetase cofactor p38 is required for lung cell differentiation". Nat. Genet. 34 (3): 330–6. doi:10.1038/ng1182. PMID 12819782. 
  15. ^ Faccio L, Fusco C, Chen A, Martinotti S, Bonventre JV, Zervos AS (January 2000). "Characterization of a novel human serine protease that has extensive homology to bacterial heat shock endoprotease HtrA and is regulated by kidney ischemia". J. Biol. Chem. 275 (4): 2581–8. PMID 10644717. 
  16. ^ Ku NO, Azhar S, Omary MB (March 2002). "Keratin 8 phosphorylation by p38 kinase regulates cellular keratin filament reorganization: modulation by a keratin 1-like disease causing mutation". J. Biol. Chem. 277 (13): 10775–82. doi:10.1074/jbc.M107623200. PMID 11788583. 
  17. ^ a b Sanz-Moreno V, Casar B, Crespo P (May 2003). "p38alpha isoform Mxi2 binds to extracellular signal-regulated kinase 1 and 2 mitogen-activated protein kinase and regulates its nuclear activity by sustaining its phosphorylation levels". Mol. Cell. Biol. 23 (9): 3079–90. PMC 153192. PMID 12697810. 
  18. ^ Raingeaud J, Whitmarsh AJ, Barrett T, Dérijard B, Davis RJ (March 1996). "MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway". Mol. Cell. Biol. 16 (3): 1247–55. PMC 231107. PMID 8622669. 
  19. ^ Stein B, Brady H, Yang MX, Young DB, Barbosa MS (May 1996). "Cloning and characterization of MEK6, a novel member of the mitogen-activated protein kinase kinase cascade". J. Biol. Chem. 271 (19): 11427–33. PMID 8626699. 
  20. ^ Ge B, Gram H, Di Padova F, Huang B, New L, Ulevitch RJ et al. (February 2002). "MAPKK-independent activation of p38alpha mediated by TAB1-dependent autophosphorylation of p38alpha". Science 295 (5558): 1291–4. doi:10.1126/science.1067289. PMID 11847341. 
  21. ^ Janknecht R (November 2001). "Cell type-specific inhibition of the ETS transcription factor ER81 by mitogen-activated protein kinase-activated protein kinase 2". J. Biol. Chem. 276 (45): 41856–61. doi:10.1074/jbc.M106630200. PMID 11551945. 
  22. ^ Zhao M, New L, Kravchenko VV, Kato Y, Gram H, di Padova F et al. (January 1999). "Regulation of the MEF2 family of transcription factors by p38". Mol. Cell. Biol. 19 (1): 21–30. PMC 83862. PMID 9858528. 
  23. ^ Yang SH, Galanis A, Sharrocks AD (June 1999). "Targeting of p38 mitogen-activated protein kinases to MEF2 transcription factors". Mol. Cell. Biol. 19 (6): 4028–38. PMC 104362. PMID 10330143. 
  24. ^ Pierrat B, Correia JS, Mary JL, Tomás-Zuber M, Lesslauer W (November 1998). "RSK-B, a novel ribosomal S6 kinase family member, is a CREB kinase under dominant control of p38alpha mitogen-activated protein kinase (p38alphaMAPK)". J. Biol. Chem. 273 (45): 29661–71. PMID 9792677. 
  25. ^ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. 

Further reading[edit]

  • Ben-Levy R, Hooper S, Wilson R, Paterson HF, Marshall CJ (1999). "Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2". Curr. Biol. 8 (19): 1049–57. doi:10.1016/S0960-9822(98)70442-7. PMID 9768359. 
  • Bradham C, McClay DR (2006). "p38 MAPK in development and cancer". Cell Cycle 5 (8): 824–8. doi:10.4161/cc.5.8.2685. PMID 16627995. 

External links[edit]