Wikipedia

MAP2K4

(Redirected fromMKK4)
Main article:Mitogen-activated protein kinase kinase

Dual-specificity mitogen-activated protein kinase kinase 4is anenzymethat in humans is encoded by theMAP2K4gene.[5]

MAP2K4
Available structures
PDBOrtholog search:PDBeRCSB
Identifiers
AliasesMAP2K4,JNKK, JNKK1, MAPKK4, MEK4, MKK4, PRKMK4, SAPKK-1, SAPKK1, SEK1, SERK1, SKK1, mitogen-activated protein kinase kinase 4
External IDsOMIM:601335;MGI:1346869;HomoloGene:48159;GeneCards:MAP2K4;OMA:MAP2K4 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

6416

26398

Ensembl

ENSG00000065559

ENSMUSG00000033352

UniProt

P45985

P47809

RefSeq (mRNA)

NM_001281435
NM_003010

RefSeq (protein)

NP_001268364
NP_003001

Location (UCSC)Chr 17: 12.02 – 12.14 MbChr 11: 65.58 – 65.68 Mb
PubMedsearch[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

MAP2K4encodes adual-specificity kinasethat belongs to theSer/Thr protein kinase family.MAP2K4 phosphorylatesMAP kinasesin response to various environmental stresses or mitogenic stimuli.MAPK8/JNK1,MAPK9/JNK2, andMAPK14/p38 are substrates for MAP2K4, but MAPK1/ERK2 and MAPK3/ERK1 are not phosphorylated by MAP2K4. Structurally, MAP2K4 contains akinasedomain that is phosphorylated and activated byMAP3K1(aka MEKK1).[6]MAP2K4 contains multipleamino acidsites that arephosphorylatedandubiquitinated.[7]Genetic studies usingMap2k4knockout mice revealed embryonic lethality, impaired hepatogenesis and defective liver formation.[8][9]Analysis of chimeric mice identified a role forMap2k4in T cell cytokine production and proliferation.[10]Map2k4-deficient chimeric mice frequently developlymphadenopathy.[11]MAP2K4 is altered in 1.97% of all human cancers.[12]

Interactions

edit

MAP2K4 has been shown tointeractwith:


References

edit
  1. ^abcGRCh38: Ensembl release 89: ENSG00000065559–Ensembl,May 2017
  2. ^abcGRCm38: Ensembl release 89: ENSMUSG00000033352–Ensembl,May 2017
  3. ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^Lin A, Minden A, Martinetto H, Claret FX, Lange-Carter C, Mercurio F, et al. (April 1995). "Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2".Science.268(5208): 286–90.Bibcode:1995Sci...268..286L.doi:10.1126/science.7716521.PMID7716521.
  6. ^"P45985 | SWISS-MODEL Repository".
  7. ^"MKK4 (human)".phosphosite.org.Retrieved2020-10-28.
  8. ^Nishina H, Vaz C, Billia P, Nghiem M, Sasaki T, De la Pompa JL, et al. (February 1999). "Defective liver formation and liver cell apoptosis in mice lacking the stress signaling kinase SEK1/MKK4".Development.126(3): 505–16.doi:10.1242/dev.126.3.505.PMID9876179.
  9. ^Ganiatsas S, Kwee L, Fujiwara Y, Perkins A, Ikeda T, Labow MA, Zon LI (June 1998)."SEK1 deficiency reveals mitogen-activated protein kinase cascade crossregulation and leads to abnormal hepatogenesis".Proceedings of the National Academy of Sciences of the United States of America.95(12): 6881–6.Bibcode:1998PNAS...95.6881G.doi:10.1073/pnas.95.12.6881.PMC22670.PMID9618507.
  10. ^Nishina H, Bachmann M, Oliveira-dos-Santos AJ, Kozieradzki I, Fischer KD, Odermatt B, et al. (September 1997)."Impaired CD28-mediated interleukin 2 production and proliferation in stress kinase SAPK/ERK1 kinase (SEK1)/mitogen-activated protein kinase kinase 4 (MKK4)-deficient T lymphocytes".The Journal of Experimental Medicine.186(6): 941–53.doi:10.1084/jem.186.6.941.PMC2199046.PMID9294148.
  11. ^Swat W, Fujikawa K, Ganiatsas S, Yang D, Xavier RJ, Harris NL, et al. (May 1998)."SEK1/MKK4 is required for maintenance of a normal peripheral lymphoid compartment but not for lymphocyte development".Immunity.8(5): 625–34.doi:10.1016/s1074-7613(00)80567-1.PMID9620683.
  12. ^"MAP2K4 - My Cancer Genome".mycancergenome.org.Retrieved2020-12-26.
  13. ^Xia Y, Wu Z, Su B, Murray B, Karin M (November 1998)."JNKK1 organizes a MAP kinase module through specific and sequential interactions with upstream and downstream components mediated by its amino-terminal extension".Genes & Development.12(21): 3369–81.doi:10.1101/gad.12.21.3369.PMC317229.PMID9808624.
  14. ^Marti A, Luo Z, Cunningham C, Ohta Y, Hartwig J, Stossel TP, et al. (January 1997)."Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor- Alpha activation of SAPK in melanoma cells".The Journal of Biological Chemistry.272(5): 2620–8.doi:10.1074/jbc.272.5.2620.PMID9006895.
  15. ^Lee CM, Onésime D, Reddy CD, Dhanasekaran N, Reddy EP (October 2002)."JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors".Proceedings of the National Academy of Sciences of the United States of America.99(22): 14189–94.Bibcode:2002PNAS...9914189L.doi:10.1073/pnas.232310199.PMC137859.PMID12391307.
  16. ^abPark 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".The Journal of Biological Chemistry.277(4): 2573–8.doi:10.1074/jbc.M110299200.PMID11707464.
  17. ^Chen Z, Cobb MH (May 2001)."Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2".The Journal of Biological Chemistry.276(19): 16070–5.doi:10.1074/jbc.M100681200.PMID11279118.
  18. ^Tournier C, Whitmarsh AJ, Cavanagh J, Barrett T, Davis RJ (July 1997)."Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase".Proceedings of the National Academy of Sciences of the United States of America.94(14): 7337–42.Bibcode:1997PNAS...94.7337T.doi:10.1073/pnas.94.14.7337.PMC23822.PMID9207092.
  19. ^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".Molecular and Cellular Biology.20(7): 2334–42.doi:10.1128/MCB.20.7.2334-2342.2000.PMC85399.PMID10713157.
  20. ^Ito M, Yoshioka K, Akechi M, Yamashita S, Takamatsu N, Sugiyama K, et al. (November 1999)."JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway".Molecular and Cellular Biology.19(11): 7539–48.doi:10.1128/mcb.19.11.7539.PMC84763.PMID10523642.
  21. ^Matsuura H, Nishitoh H, Takeda K, Matsuzawa A, Amagasa T, Ito M, et al. (October 2002)."Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway. A new mode of regulation of the MAP kinase cascade".The Journal of Biological Chemistry.277(43): 40703–9.doi:10.1074/jbc.M202004200.hdl:2297/2692.PMID12189133.
  22. ^Ahn YH, Kurie JM (October 2009)."MKK4/SEK1 is negatively regulated through a feedback loop involving the E3 ubiquitin ligase itch".The Journal of Biological Chemistry.284(43): 29399–29404.doi:10.1074/jbc.M109.044958.PMC2785572.PMID19737936.

Further reading

edit
  • Lin, A (2006). "The JNK Signaling Pathway (Molecular Biology Intelligence Unit)".Landes Bioscience.1:1–97.ISBN978-1587061202.
Retrieved from "https://en.wikipedia.org/w/index.php?title=MAP2K4&oldid=1213117658"