The protein encoded by this gene is a member of the MAP kinase and JNK 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 cell stimuli, and targets specific transcription factors, and thus mediates immediate-early gene expression in response to cell stimuli. The activation of this kinase by tumor-necrosis factor alpha (TNF-alpha) is found to be required for TNF-alpha-induced apoptosis. This kinase is also involved in UV radiation-induced apoptosis, which is thought to be related to the cytochrome c-mediated cell death pathway. Studies of the mouse counterpart of this gene suggested that this kinase play a key role in T cell proliferation, apoptosis and differentiation. Four alternately spliced transcript variants encoding distinct isoforms have been reported.[3]
↑ 1.01.1Dérijard B, Hibi M, Wu IH, Barrett T, Su B, Deng T, Karin M, Davis RJ (April 1994). "JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain". Cell. 76 (6): 1025–37. doi:10.1016/0092-8674(94)90380-8. PMID8137421.
↑Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ, Davis RJ (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. doi:10.1074/jbc.270.13.7420. PMID7535770.
↑Fuchs SY, Xie B, Adler V, Fried VA, Davis RJ, Ronai Z (December 1997). "c-Jun NH2-terminal kinases target the ubiquitination of their associated transcription factors". J. Biol. Chem. 272 (51): 32163–8. doi:10.1074/jbc.272.51.32163. PMID9405416.
↑ 6.06.1Chen 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. PMID11279118.
↑ 8.08.1Meyer CF, Wang X, Chang C, Templeton D, Tan TH (April 1996). "Interaction between c-Rel and the mitogen-activated protein kinase kinase kinase 1 signaling cascade in mediating kappaB enhancer activation". J. Biol. Chem. 271 (15): 8971–6. doi:10.1074/jbc.271.15.8971. PMID8621542.
↑Nishitoh H, Saitoh M, Mochida Y, Takeda K, Nakano H, Rothe M, Miyazono K, Ichijo H (September 1998). "ASK1 is essential for JNK/SAPK activation by TRAF2". Mol. Cell. 2 (3): 389–95. doi:10.1016/s1097-2765(00)80283-x. PMID9774977.
↑Yazgan O, Pfarr CM (August 2002). "Regulation of two JunD isoforms by Jun N-terminal kinases". J. Biol. Chem. 277 (33): 29710–8. doi:10.1074/jbc.M204552200. PMID12052834.
↑Tada K, Okazaki T, Sakon S, Kobarai T, Kurosawa K, Yamaoka S, Hashimoto H, Mak TW, Yagita H, Okumura K, Yeh WC, Nakano H (September 2001). "Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death". J. Biol. Chem. 276 (39): 36530–4. doi:10.1074/jbc.M104837200. PMID11479302.
↑Cano E, Hazzalin CA, Kardalinou E, Buckle RS, Mahadevan LC (November 1995). "Neither ERK nor JNK/SAPK MAP kinase subtypes are essential for histone H3/HMG-14 phosphorylation or c-fos and c-jun induction". J. Cell Sci. 108 (11): 3599–609. PMID8586671.
↑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. doi:10.1074/jbc.274.28.19949. PMID10391943.
↑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. PMID11278799.
↑Wang T, Arifoglu P, Ronai Z, Tew KD (June 2001). "Glutathione S-transferase P1-1 (GSTP1-1) inhibits c-Jun N-terminal kinase (JNK1) signaling through interaction with the C terminus". J. Biol. Chem. 276 (24): 20999–1003. doi:10.1074/jbc.M101355200. PMID11279197.
↑Aguirre V, Werner ED, Giraud J, Lee YH, Shoelson SE, White MF (January 2002). "Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action". J. Biol. Chem. 277 (2): 1531–7. doi:10.1074/jbc.M101521200. PMID11606564.
↑Aguirre V, Uchida T, Yenush L, Davis R, White MF (March 2000). "The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307)". J. Biol. Chem. 275 (12): 9047–54. doi:10.1074/jbc.275.12.9047. PMID10722755.
↑Park HS, Kim MS, Huh SH, Park J, Chung J, Kang SS, Choi EJ (January 2002). "Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation". J. Biol. Chem. 277 (4): 2573–8. doi:10.1074/jbc.M110299200. PMID11707464.
↑Xu S, Cobb MH (December 1997). "MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases". J. Biol. Chem. 272 (51): 32056–60. doi:10.1074/jbc.272.51.32056. PMID9405400.
↑Cai Y, Lechner MS, Nihalani D, Prindle MJ, Holzman LB, Dressler GR (January 2002). "Phosphorylation of Pax2 by the c-Jun N-terminal kinase and enhanced Pax2-dependent transcription activation". J. Biol. Chem. 277 (2): 1217–22. doi:10.1074/jbc.M109663200. PMID11700324.
↑Noguchi K, Kitanaka C, Yamana H, Kokubu A, Mochizuki T, Kuchino Y (November 1999). "Regulation of c-Myc through phosphorylation at Ser-62 and Ser-71 by c-Jun N-terminal kinase". J. Biol. Chem. 274 (46): 32580–7. doi:10.1074/jbc.274.46.32580. PMID10551811.
Liu J, Lin A (2007). "Wiring the cell signaling circuitry by the NF-kappa B and JNK1 crosstalk and its applications in human diseases". Oncogene. 26 (22): 3267–78. doi:10.1038/sj.onc.1210417. PMID17496921.
1jnk: THE C-JUN N-TERMINAL KINASE (JNK3S) COMPLEXED WITH MGAMP-PNP
PDB 1pmn EBI.jpg
1pmn: Crystal structure of JNK3 in complex with an imidazole-pyrimidine inhibitor
PDB 1pmq EBI.jpg
1pmq: The structure of JNK3 in complex with an imidazole-pyrimidine inhibitor
PDB 1pmu EBI.jpg
1pmu: The crystal structure of JNK3 in complex with a phenantroline inhibitor
PDB 1pmv EBI.jpg
1pmv: The structure of JNK3 in complex with a dihydroanthrapyrazole inhibitor
PDB 1ukh EBI.jpg
1ukh: Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125
PDB 1uki EBI.jpg
1uki: Structural basis for the selective inhibition of JNK1 by the scaffolding protein JIP1 and SP600125
PDB 2b1p EBI.jpg
2b1p: inhibitor complex of JNK3
PDB 2exc EBI.jpg
2exc: Inhibitor complex of JNK3
PDB 2g01 EBI.png
2g01: Pyrazoloquinolones as Novel, Selective JNK1 inhibitors
PDB 2gmx EBI.png
2gmx: Selective Aminopyridine-Based C-Jun N-terminal Kinase inhibitors with cellular activity
PDB 2h96 EBI.png
2h96: Discovery of Potent, Highly Selective, and Orally Bioavailable Pyridine Carboxamide C-jun NH2-terminal Kinase Inhibitors
PDB 2no3 EBI.png
2no3: Novel 4-anilinopyrimidines as potent JNK1 Inhibitors
PDB 2o0u EBI.jpg
2o0u: Crystal structure of human JNK3 complexed with N-{3-cyano-6-[3-(1-piperidinyl)propanoyl]-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-2-yl}-1-naphthalenecarboxamide
PDB 2o2u EBI.jpg
2o2u: Crystal structure of human JNK3 complexed with N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)-2-fluorobenzamide
PDB 2ok1 EBI.jpg
2ok1: Crystal structure of JNK3 bound to N-benzyl-4-(4-(3-chlorophenyl)-1H-pyrazol-3-yl)-1H-pyrrole-2-carboxamide