MAP3K14 explained

Mitogen-activated protein kinase kinase kinase 14 (MAP3K14), also known as NF-kappa-B-inducing kinase (NIK), is a MAP kinase kinase kinase enzyme that in humans is encoded by the MAP3K14 gene.^{[1] [2]}

Function

This gene encodes mitogen-activated protein kinase kinase kinase 14, NIK, which is a serine/threonine protein-kinase. This kinase binds to TRAF2 and stimulates NF-κB activity. It is a critical kinase of the alternative NF-κB activation pathway. It shares sequence similarity with several other MAPKK kinases. It participates in an NF-κB-inducing signalling cascade common to receptors of the tumour-necrosis/nerve-growth factor (TNF/NGF) family and to the interleukin-1 type-I receptor.

Interactions

MAP3K14 has been shown to interact with:

• CHUK,^{[3] [4] [5]}
• IKK2,^[6] and
• TRAF2.^[7]

Further reading

• Régnier CH, Song HY, Gao X, Goeddel DV, Cao Z, Rothe M . Identification and characterization of an IkappaB kinase . Cell . 90 . 2 . 373–83 . 1997 . 9244310 . 10.1016/S0092-8674(00)80344-X . 16217708 . free .
• Song HY, Régnier CH, Kirschning CJ, Goeddel DV, Rothe M . Tumor necrosis factor (TNF)-mediated kinase cascades: Bifurcation of Nuclear Factor-κB and c-jun N-terminal kinase (JNK/SAPK) pathways at TNF receptor-associated factor 2 . Proc. Natl. Acad. Sci. U.S.A. . 94 . 18 . 9792–6 . 1997 . 9275204 . 23270 . 10.1073/pnas.94.18.9792 . 1997PNAS...94.9792S . free .
• Woronicz JD, Gao X, Cao Z, Rothe M, Goeddel DV . IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK . Science . 278 . 5339 . 866–9 . 1997 . 9346485 . 10.1126/science.278.5339.866 . 1997Sci...278..866W .
• Ling L, Cao Z, Goeddel DV . NF-κB-inducing kinase activates IKK-α by phosphorylation of Ser-176 . Proc. Natl. Acad. Sci. U.S.A. . 95 . 7 . 3792–7 . 1998 . 9520446 . 19916 . 10.1073/pnas.95.7.3792 . 1998PNAS...95.3792L . free .
• Lee FS, Peters RT, Dang LC, Maniatis T . MEKK1 activates both IκB kinase α and IκB kinase β . Proc. Natl. Acad. Sci. U.S.A. . 95 . 16 . 9319–24 . 1998 . 9689078 . 21336 . 10.1073/pnas.95.16.9319 . 1998PNAS...95.9319L . free .
• Lin X, Mu Y, Cunningham ET, Marcu KB, Geleziunas R, Greene WC . Molecular Determinants of NF-κB-Inducing Kinase Action . Mol. Cell. Biol. . 18 . 10 . 5899–907 . 1998 . 9742107 . 109176 . 10.1128/mcb.18.10.5899.
• Cohen L, Henzel WJ, Baeuerle PA . IKAP is a scaffold protein of the IkappaB kinase complex . Nature . 395 . 6699 . 292–6 . 1998 . 9751059 . 10.1038/26254 . 1998Natur.395..292C . 4327300 .
• Aronsson FC, Magnusson P, Andersson B, Karsten SL, Shibasaki Y, Lendon CL, Goate AM, Brookes AJ . The NIK protein kinase and C17orf1 genes: chromosomal mapping, gene structures and mutational screening in frontotemporal dementia and parkinsonism linked to chromosome 17 . Hum. Genet. . 103 . 3 . 340–5 . 1998 . 9799091 . 10.1007/s004390050827 . 11305597 .
• Nemoto S, DiDonato JA, Lin A . Coordinate Regulation of IκB Kinases by Mitogen-Activated Protein Kinase Kinase Kinase 1 and NF-κB-Inducing Kinase . Mol. Cell. Biol. . 18 . 12 . 7336–43 . 1998 . 9819420 . 109315 . 10.1128/mcb.18.12.7336.
• Li Y, Kang J, Friedman J, Tarassishin L, Ye J, Kovalenko A, Wallach D, Horwitz MS . Identification of a cell protein (FIP-3) as a modulator of NF-κB activity and as a target of an adenovirus inhibitor of tumor necrosis factor α-induced apoptosis . Proc. Natl. Acad. Sci. U.S.A. . 96 . 3 . 1042–7 . 1999 . 9927690 . 15347 . 10.1073/pnas.96.3.1042 . 1999PNAS...96.1042L . free .
• Lallena MJ, Diaz-Meco MT, Bren G, Payá CV, Moscat J . Activation of IκB Kinase β by Protein Kinase C Isoforms . Mol. Cell. Biol. . 19 . 3 . 2180–8 . 1999 . 10022904 . 84010 . 10.1128/MCB.19.3.2180.
• Lin X, Cunningham ET, Mu Y, Geleziunas R, Greene WC . The proto-oncogene Cot kinase participates in CD3/CD28 induction of NF-kappaB acting through the NF-kappaB-inducing kinase and IkappaB kinases . Immunity . 10 . 2 . 271–80 . 1999 . 10072079 . 10.1016/S1074-7613(00)80027-8 . free .
• Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K . The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway . Nature . 398 . 6724 . 252–6 . 1999 . 10094049 . 10.1038/18465 . 1999Natur.398..252N . 4421236 .
• Delhase M, Hayakawa M, Chen Y, Karin M . Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation . Science . 284 . 5412 . 309–13 . 1999 . 10195894 . 10.1126/science.284.5412.309 .
• Hu WH, Johnson H, Shu HB . Tumor necrosis factor-related apoptosis-inducing ligand receptors signal NF-kappaB and JNK activation and apoptosis through distinct pathways . J. Biol. Chem. . 274 . 43 . 30603–10 . 1999 . 10521444 . 10.1074/jbc.274.43.30603 . free .
• Richard Gaynor. Yamamoto Y, Yin MJ, Gaynor RB . IκB Kinase α (IKKα) Regulation of IKKβ Kinase Activity . Mol. Cell. Biol. . 20 . 10 . 3655–66 . 2000 . 10779355 . 85658 . 10.1128/MCB.20.10.3655-3666.2000 .
• Xiao G, Sun SC . Negative regulation of the nuclear factor kappa B-inducing kinase by a cis-acting domain . J. Biol. Chem. . 275 . 28 . 21081–5 . 2000 . 10887201 . 10.1074/jbc.M002552200 . free .
• Chaudhary PM, Eby MT, Jasmin A, Kumar A, Liu L, Hood L . Activation of the NF-kappaB pathway by caspase 8 and its homologs . Oncogene . 19 . 39 . 4451–60 . 2000 . 11002417 . 10.1038/sj.onc.1203812 . free .
• Kumar A, Eby MT, Sinha S, Jasmin A, Chaudhary PM . The ectodermal dysplasia receptor activates the nuclear factor-kappaB, JNK, and cell death pathways and binds to ectodysplasin A . J. Biol. Chem. . 276 . 4 . 2668–77 . 2001 . 11035039 . 10.1074/jbc.M008356200 . free .

Notes and References

1. Malinin NL, Boldin MP, Kovalenko AV, Wallach D . MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1 . Nature . 385 . 6616 . 540–4 . March 1997 . 9020361 . 10.1038/385540a0 . 4366355 .
2. Web site: Entrez Gene: MAP3K14 mitogen-activated protein ki kinase kinase 14.
3. Régnier CH, Song HY, Gao X, Goeddel DV, Cao Z, Rothe M . Identification and characterization of an IkappaB kinase . Cell . 90 . 2 . 373–83 . July 1997 . 9244310 . 10.1016/S0092-8674(00)80344-X. 16217708 . free .
4. Xiao G, Sun SC . Negative regulation of the nuclear factor kappa B-inducing kinase by a cis-acting domain . J. Biol. Chem. . 275 . 28 . 21081–5 . July 2000 . 10887201 . 10.1074/jbc.M002552200 . free .
5. Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K . The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway . Nature . 398 . 6724 . 252–6 . March 1999 . 10094049 . 10.1038/18465 . 1999Natur.398..252N . 4421236 .
6. Woronicz JD, Gao X, Cao Z, Rothe M, Goeddel DV . IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK . Science . 278 . 5339 . 866–9 . October 1997 . 9346485 . 10.1126/science.278.5339.866. 1997Sci...278..866W .
7. Luftig MA, Cahir-McFarland E, Mosialos G, Kieff E . Effects of the NIK aly mutation on NF-kappaB activation by the Epstein-Barr virus latent infection membrane protein, lymphotoxin beta receptor, and CD40 . J. Biol. Chem. . 276 . 18 . 14602–6 . May 2001 . 11278268 . 10.1074/jbc.C100103200 . free .