MAPK8

Mitogen-activated protein kinase 8
	; PDB rendering based on 1jnk.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1UKH, 1UKI, 2G01, 2GMX, 2H96, 2NO3, 2XRW, 2XS0, 3ELJ, 3O17, 3O2M, 3PZE, 3V3V, 3VUD, 3VUG, 3VUH, 3VUI, 3VUK, 3VUL, 3VUM, 4AWI
Identifiers
Symbols	MAPK8; JNK; JNK-46; JNK1; JNK1A2; JNK21B1/2; PRKM8; SAPK1; SAPK1c
External IDs	OMIM: 601158 MGI: 1346861 HomoloGene: 56760 ChEMBL: 2276 GeneCards: MAPK8 Gene
EC number	2.7.11.24
Gene Ontology
Molecular function	• protein serine/threonine kinase activity; • JUN kinase activity; • protein binding; • ATP binding; • histone deacetylase regulator activity; • histone deacetylase binding;
Cellular component	• nucleus; • nucleoplasm; • mitochondrion; • cytosol;
Biological process	• ossification; • toll-like receptor signaling pathway; • MyD88-dependent toll-like receptor signaling pathway; • MyD88-independent toll-like receptor signaling pathway; • apoptotic process; • response to stress; • JNK cascade; • JUN phosphorylation; • response to UV; • positive regulation of gene expression; • peptidyl-serine phosphorylation; • peptidyl-threonine phosphorylation; • regulation of histone deacetylation; • negative regulation of protein binding; • regulation of protein localization; • toll-like receptor 2 signaling pathway; • toll-like receptor 3 signaling pathway; • toll-like receptor 4 signaling pathway; • toll-like receptor 5 signaling pathway; • toll-like receptor 9 signaling pathway; • toll-like receptor 10 signaling pathway; • TRIF-dependent toll-like receptor signaling pathway; • toll-like receptor TLR1:TLR2 signaling pathway; • toll-like receptor TLR6:TLR2 signaling pathway; • negative regulation of apoptotic process; • innate immune response; • response to cadmium ion; • neurotrophin TRK receptor signaling pathway; • regulation of sequence-specific DNA binding transcription factor activity; • stress-activated MAPK cascade; • cellular response to mechanical stimulus; • positive regulation of deacetylase activity; • apoptotic signaling pathway; • intrinsic apoptotic signaling pathway; • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; • positive regulation of determination of dorsal identity; • positive regulation of apoptotic signaling pathway;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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Mitogen-activated protein kinase 8 (also known as JNK1) is an enzyme that in humans is encoded by the MAPK8 gene.¹²

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

Interactions

MAPK8 has been shown to interact with SPIB,⁴ DUSP1,⁵ Activating transcription factor 2,⁶⁷⁸⁹ SH3BP5,¹⁰ GSTP1,¹¹ MAPK8IP1,¹²¹³ MAP2K7,⁹¹⁴ CRK,¹⁵ MAP2K4,⁸⁹¹⁴¹⁶¹⁷ DUSP22,¹⁸ Myc,¹⁹ MAP3K2,¹⁴ DUSP10,²⁰ REL,²¹ MAPK8IP3,²²²³ IRS1,²⁴²⁵ MAP3K1²⁶ and C-jun.¹⁹²¹²⁷²⁸²⁹³⁰³¹

References

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^ ^a ^b ^c ^d Tournier, C; Whitmarsh A J, Cavanagh J, Barrett T, Davis R J (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. (UNITED STATES) 94 (14): 7337–42. doi:10.1073/pnas.94.14.7337. ISSN 0027-8424. PMC 23822. PMID 9207092.
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^ Wang, T; Arifoglu P, Ronai Z, Tew K D (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. (United States) 276 (24): 20999–1003. doi:10.1074/jbc.M101355200. ISSN 0021-9258. PMID 11279197.
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^ ^a ^b ^c Cheng, J; Yang J, Xia Y, Karin M, Su B (April 2000). "Synergistic Interaction of MEK Kinase 2, c-Jun N-Terminal Kinase (JNK) Kinase 2, and JNK1 Results in Efficient and Specific JNK1 Activation". Mol. Cell. Biol. (UNITED STATES) 20 (7): 2334–42. doi:10.1128/MCB.20.7.2334-2342.2000. ISSN 0270-7306. PMC 85399. PMID 10713157.
^ Girardin, S E; Yaniv M (July 2001). "A direct interaction between JNK1 and CrkII is critical for Rac1-induced JNK activation". EMBO J. (England) 20 (13): 3437–46. doi:10.1093/emboj/20.13.3437. ISSN 0261-4189. PMC 125507. PMID 11432831.
^ Lee, Clement M; Onésime Djamila, Reddy C Damodara, Dhanasekaran N, Reddy E Premkumar (October 2002). "JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors". Proc. Natl. Acad. Sci. U.S.A. (United States) 99 (22): 14189–94. doi:10.1073/pnas.232310199. ISSN 0027-8424. PMC 137859. PMID 12391307.
^ Park, Hee-Sae; Kim Mi-Sung, Huh Sung-Ho, Park Jihyun, Chung Jongkyeong, Kang Sang Sun, Choi Eui-Ju (January 2002). "Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation". J. Biol. Chem. (United States) 277 (4): 2573–8. doi:10.1074/jbc.M110299200. ISSN 0021-9258. PMID 11707464.
^ Aoyama, K; Nagata M, Oshima K, Matsuda T, Aoki N (July 2001). "Molecular cloning and characterization of a novel dual specificity phosphatase, LMW-DSP2, that lacks the cdc25 homology domain". J. Biol. Chem. (United States) 276 (29): 27575–83. doi:10.1074/jbc.M100408200. ISSN 0021-9258. PMID 11346645.
^ 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. (UNITED STATES) 274 (46): 32580–7. doi:10.1074/jbc.274.46.32580. ISSN 0021-9258. PMID 10551811.
^ Tanoue, T; Moriguchi T, Nishida E (July 1999). "Molecular cloning and characterization of a novel dual specificity phosphatase, MKP-5". J. Biol. Chem. (UNITED STATES) 274 (28): 19949–56. doi:10.1074/jbc.274.28.19949. ISSN 0021-9258. PMID 10391943.
^ ^a ^b Meyer, C F; Wang X, Chang C, Templeton D, Tan T H (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. (UNITED STATES) 271 (15): 8971–6. doi:10.1074/jbc.271.15.8971. ISSN 0021-9258. PMID 8621542.
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^ Aguirre, Vincent; Werner Eric D, Giraud Jodel, Lee Yong Hee, Shoelson Steve E, White Morris F (January 2002). "Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action". J. Biol. Chem. (United States) 277 (2): 1531–7. doi:10.1074/jbc.M101521200. ISSN 0021-9258. PMID 11606564.
^ Aguirre, V; Uchida T, Yenush L, Davis R, White M F (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. (UNITED STATES) 275 (12): 9047–54. doi:10.1074/jbc.275.12.9047. ISSN 0021-9258. PMID 10722755.
^ Xu, S; Cobb M H (December 1997). "MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases". J. Biol. Chem. (UNITED STATES) 272 (51): 32056–60. doi:10.1074/jbc.272.51.32056. ISSN 0021-9258. PMID 9405400.
^ Ishitani, Tohru; Takaesu Giichi, Ninomiya-Tsuji Jun, Shibuya Hiroshi, Gaynor Richard B, Matsumoto Kunihiro (December 2003). "Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling". EMBO J. (England) 22 (23): 6277–88. doi:10.1093/emboj/cdg605. ISSN 0261-4189. PMC 291846. PMID 14633987.
^ 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 (UNITED STATES) 2 (3): 389–95. doi:10.1016/S1097-2765(00)80283-X. ISSN 1097-2765. PMID 9774977.
^ Yazgan, Oya; Pfarr Curt M (August 2002). "Regulation of two JunD isoforms by June N-terminal kinases". J. Biol. Chem. (United States) 277 (33): 29710–8. doi:10.1074/jbc.M204552200. ISSN 0021-9258. PMID 12052834.
^ Tada, K; Okazaki T, Sakon S, Kobarai T, Kurosawa K, Yamaoka S, Hashimoto H, Mak T W, Yagita H, Okumura K, Yeh W C, 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. (United States) 276 (39): 36530–4. doi:10.1074/jbc.M104837200. ISSN 0021-9258. PMID 11479302.
^ Cano, E; Hazzalin C A, Kardalinou E, Buckle R S, Mahadevan L C (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. (ENGLAND) 108 (11): 3599–609. ISSN 0021-9533. PMID 8586671.

External links

MAP Kinase Resource .

MAPK8

Contents

Interactions

References

External links

Further reading