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 most closely related to p38 MAP kinase, both of which can be activated by proinflammatory cytokines and environmental stress. This kinase is activated through its phosphorylation by MAP kinase kinases (MKKs), preferably by MKK6. Transcription factorATF2/CREB2 has been shown to be a substrate of this kinase.[2]
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↑Shin J, Park B, Cho S, Lee S, Kim Y, Lee SO, Cho K, Lee S, Jin BS, Ahn JH, Choi EJ, Ahn K (Sep 2004). "Promyelocytic leukemia is a direct inhibitor of SAPK2/p38 mitogen-activated protein kinase". J. Biol. Chem. 279 (39): 40994–1003. doi:10.1074/jbc.M407369200. PMID15273249.
Jiang Y, Chen C, Li Z, Guo W, Gegner JA, Lin S, Han J (1996). "Characterization of the structure and function of a new mitogen-activated protein kinase (p38beta)". J. Biol. Chem. 271 (30): 17920–6. doi:10.1074/jbc.271.30.17920. PMID8663524.
Kumar S, McDonnell PC, Gum RJ, Hand AT, Lee JC, Young PR (1997). "Novel homologues of CSBP/p38 MAP kinase: activation, substrate specificity and sensitivity to inhibition by pyridinyl imidazoles". Biochem. Biophys. Res. Commun. 235 (3): 533–8. doi:10.1006/bbrc.1997.6849. PMID9207191.
Stein B, Yang MX, Young DB, Janknecht R, Hunter T, Murray BW, Barbosa MS (1997). "p38-2, a novel mitogen-activated protein kinase with distinct properties". J. Biol. Chem. 272 (31): 19509–17. doi:10.1074/jbc.272.31.19509. PMID9235954.
Enslen H, Raingeaud J, Davis RJ (1998). "Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6". J. Biol. Chem. 273 (3): 1741–8. doi:10.1074/jbc.273.3.1741. PMID9430721.
Tanoue T, Yamamoto T, Maeda R, Nishida E (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. PMID11359773.
Torcia M, De Chiara G, Nencioni L, Ammendola S, Labardi D, Lucibello M, Rosini P, Marlier LN, Bonini P, Dello Sbarba P, Palamara AT, Zambrano N, Russo T, Garaci E, Cozzolino F (2001). "Nerve growth factor inhibits apoptosis in memory B lymphocytes via inactivation of p38 MAPK, prevention of Bcl-2 phosphorylation, and cytochrome c release". J. Biol. Chem. 276 (42): 39027–36. doi:10.1074/jbc.M102970200. PMID11495898.
Ge B, Gram H, Di Padova F, Huang B, New L, Ulevitch RJ, Luo Y, Han J (2002). "MAPKK-independent activation of p38alpha mediated by TAB1-dependent autophosphorylation of p38alpha". Science. 295 (5558): 1291–4. doi:10.1126/science.1067289. PMID11847341.
Reunanen N, Li SP, Ahonen M, Foschi M, Han J, Kähäri VM (2002). "Activation of p38 alpha MAPK enhances collagenase-1 (matrix metalloproteinase (MMP)-1) and stromelysin-1 (MMP-3) expression by mRNA stabilization". J. Biol. Chem. 277 (35): 32360–8. doi:10.1074/jbc.M204296200. PMID12060661.
Kinet S, Bernard F, Mongellaz C, Perreau M, Goldman FD, Taylor N (2002). "gp120-mediated induction of the MAPK cascade is dependent on the activation state of CD4(+) lymphocytes". Blood. 100 (7): 2546–53. doi:10.1182/blood-2002-03-0819. PMID12239168.
Lim S, Zou Y, Friedman E (2002). "The transcriptional activator Mirk/Dyrk1B is sequestered by p38alpha/beta MAP kinase". J. Biol. Chem. 277 (51): 49438–45. doi:10.1074/jbc.M206840200. PMID12384504.
Naderi J, Hung M, Pandey S (2003). "Oxidative stress-induced apoptosis in dividing fibroblasts involves activation of p38 MAP kinase and over-expression of Bax: resistance of quiescent cells to oxidative stress". Apoptosis. 8 (1): 91–100. doi:10.1023/A:1021657220843. PMID12510156.
Stringaris AK, Geisenhainer J, Bergmann F, Balshüsemann C, Lee U, Zysk G, Mitchell TJ, Keller BU, Kuhnt U, Gerber J, Spreer A, Bähr M, Michel U, Nau R (2002). "Neurotoxicity of pneumolysin, a major pneumococcal virulence factor, involves calcium influx and depends on activation of p38 mitogen-activated protein kinase". Neurobiol. Dis. 11 (3): 355–68. doi:10.1006/nbdi.2002.0561. PMID12586546.