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 targets specific transcription factors, and thus mediates immediate-early gene expression in response to various cell stimuli. It is most closely related to MAPK8, both of which are involved in UV radiation-induced apoptosis, thought to be related to the cytochrome c-mediated cell death pathway. This gene and MAPK8 are also known as c-Jun N-terminal kinases. This kinase blocks the ubiquitination of tumor suppressor p53, and thus it increases the stability of p53 in nonstressed cells. Studies of this gene's mouse counterpart suggest a key role in T-cell differentiation. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.
^Kallunki T, Su B, Tsigelny I, Sluss HK, Dérijard B, Moore G, Davis R, Karin M (Dec 1994). "JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation". Genes & Development. 8 (24): 2996–3007. doi:10.1101/gad.8.24.2996. PMID8001819.
^Saleem A, Datta R, Yuan ZM, Kharbanda S, Kufe D (Dec 1995). "Involvement of stress-activated protein kinase in the cellular response to 1-beta-D-arabinofuranosylcytosine and other DNA-damaging agents". Cell Growth & Differentiation. 6 (12): 1651–8. PMID9019171.
^Kharbanda S, Saleem A, Shafman T, Emoto Y, Taneja N, Rubin E, Weichselbaum R, Woodgett J, Avruch J, Kyriakis J (Aug 1995). "Ionizing radiation stimulates a Grb2-mediated association of the stress-activated protein kinase with phosphatidylinositol 3-kinase". The Journal of Biological Chemistry. 270 (32): 18871–4. doi:10.1074/jbc.270.32.18871. PMID7642542.
^Lin Y, Khokhlatchev A, Figeys D, Avruch J (Dec 2002). "Death-associated protein 4 binds MST1 and augments MST1-induced apoptosis". The Journal of Biological Chemistry. 277 (50): 47991–8001. doi:10.1074/jbc.M202630200. PMID12384512.
^Maekawa M, Nishida E, Tanoue T (Oct 2002). "Identification of the Anti-proliferative protein Tob as a MAPK substrate". The Journal of Biological Chemistry. 277 (40): 37783–7. doi:10.1074/jbc.M204506200. PMID12151396.
Freedman BD, Liu QH, Del Corno M, Collman RG (2004). "HIV-1 gp120 chemokine receptor-mediated signaling in human macrophages". Immunologic Research. 27 (2-3): 261–76. doi:10.1385/IR:27:2-3:261. PMID12857973.
Lee C, Liu QH, Tomkowicz B, Yi Y, Freedman BD, Collman RG (Nov 2003). "Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signaling pathways". Journal of Leukocyte Biology. 74 (5): 676–82. doi:10.1189/jlb.0503206. PMID12960231.
Denys H, Desmet R, Stragier M, Vergison R, Lemahieu SF (1978). "Cystitis emphysematosa". Acta Urologica Belgica. 45 (4): 327–31. PMID602896.
Chu Y, Solski PA, Khosravi-Far R, Der CJ, Kelly K (Mar 1996). "The mitogen-activated protein kinase phosphatases PAC1, MKP-1, and MKP-2 have unique substrate specificities and reduced activity in vivo toward the ERK2 sevenmaker mutation". The Journal of Biological Chemistry. 271 (11): 6497–501. doi:10.1074/jbc.271.11.6497. PMID8626452.
Bocco JL, Bahr A, Goetz J, Hauss C, Kallunki T, Kedinger C, Chatton B (May 1996). "In vivo association of ATFa with JNK/SAP kinase activities". Oncogene. 12 (9): 1971–80. PMID8649858.
Kallunki T, Deng T, Hibi M, Karin M (Nov 1996). "c-Jun can recruit JNK to phosphorylate dimerization partners via specific docking interactions". Cell. 87 (5): 929–39. doi:10.1016/S0092-8674(00)81999-6. PMID8945519.
Jabado N, Pallier A, Jauliac S, Fischer A, Hivroz C (Feb 1997). "gp160 of HIV or anti-CD4 monoclonal antibody ligation of CD4 induces inhibition of JNK and ERK-2 activities in human peripheral CD4+ T lymphocytes". European Journal of Immunology. 27 (2): 397–404. doi:10.1002/eji.1830270209. PMID9045910.
Chow CW, Rincón M, Cavanagh J, Dickens M, Davis RJ (Nov 1997). "Nuclear accumulation of NFAT4 opposed by the JNK signal transduction pathway". Science. 278 (5343): 1638–41. doi:10.1126/science.278.5343.1638. PMID9374467.
Lannuzel A, Barnier JV, Hery C, Huynh VT, Guibert B, Gray F, Vincent JD, Tardieu M (Dec 1997). "Human immunodeficiency virus type 1 and its coat protein gp120 induce apoptosis and activate JNK and ERK mitogen-activated protein kinases in human neurons". Annals of Neurology. 42 (6): 847–56. doi:10.1002/ana.410420605. PMID9403476.
Fuchs SY, Xie B, Adler V, Fried VA, Davis RJ, Ronai Z (Dec 1997). "c-Jun NH2-terminal kinases target the ubiquitination of their associated transcription factors". The Journal of Biological Chemistry. 272 (51): 32163–8. doi:10.1074/jbc.272.51.32163. PMID9405416.