MAP3K1: Difference between revisions

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== Disease and therapeutic targeting ==
== Disease and therapeutic targeting ==


MAP3K1 is a breast cancer susceptibility allele<ref name="pmid22722201">{{cite journal | vauthors = Stephens PJ, Tarpey PS, Davies H, Van Loo P, Greenman C, Wedge DC, Nik-Zainal S, Martin S, Varela I, Bignell GR, Yates LR, Papaemmanuil E, Beare D, Butler A, Cheverton A, Gamble J, Hinton J, Jia M, Jayakumar A, Jones D, Latimer C, Lau KW, McLaren S, McBride DJ, Menzies A, Mudie L, Raine K, Rad R, Chapman MS, Teague J, Easton D, Langerød A, Lee MT, Shen CY, Tee BT, Huimin BW, Broeks A, Vargas AC, Turashvili G, Martens J, Fatima A, Miron P, Chin SF, Thomas G, Boyault S, Mariani O, Lakhani SR, van de Vijver M, van 't Veer L, Foekens J, Desmedt C, Sotiriou C, Tutt A, Caldas C, Reis-Filho JS, Aparicio SA, Salomon AV, Børresen-Dale AL, Richardson AL, Campbell PJ, Futreal PA, Stratton MR | display-authors = 6 | title = The landscape of cancer genes and mutational processes in breast cancer | journal = Nature | volume = 486 | issue = 7403 | pages = 400–4 | date = May 2012 | pmid = 22722201 | pmc = 3428862 | doi = 10.1038/nature11017 }}</ref> and 46,XY disorders of sex development gene.<ref name="pmid21129722">{{cite journal | vauthors = Pearlman A, Loke J, Le Caignec C, White S, Chin L, Friedman A, Warr N, Willan J, Brauer D, Farmer C, Brooks E, Oddoux C, Riley B, Shajahan S, Camerino G, Homfray T, Crosby AH, Couper J, David A, Greenfield A, Sinclair A, Ostrer H | display-authors = 6 | title = Mutations in MAP3K1 cause 46,XY disorders of sex development and implicate a common signal transduction pathway in human testis determination | journal = American Journal of Human Genetics | volume = 87 | issue = 6 | pages = 898–904 | date = December 2010 | pmid = 21129722 | pmc = 2997363 | doi = 10.1016/j.ajhg.2010.11.003 }}</ref> E6201 is a chemical inhibitor of MAP3K1 that shows cross-specificity with [[MAP2K1]]. <ref name="pmid19684251">{{cite journal | vauthors = Goto M, Chow J, Muramoto K, Chiba K, Yamamoto S, Fujita M, Obaishi H, Tai K, Mizui Y, Tanaka I, Young D, Yang H, Wang YJ, Shirota H, Gusovsky F | display-authors = 6 | title = E6201 [(3S,4R,5Z,8S,9S,11E)-14-(ethylamino)-8, 9,16-trihydroxy-3,4-dimethyl-3,4,9,19-tetrahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione], a novel kinase inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-1 and MEK kinase-1: in vitro characterization of its anti-inflammatory and antihyperproliferative activities | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 331 | issue = 2 | pages = 485–95 | date = November 2009 | pmid = 19684251 | doi = 10.1124/jpet.109.156554 }}</ref>
MAP3K1 is a breast cancer susceptibility allele and 46,XY disorders of sex development gene <ref>https://www.ncbi.nlm.nih.gov/pubmed/22722201</ref> <ref>https://www.ncbi.nlm.nih.gov/pubmed/21129722</ref> . E6201 is a chemical inhibitor of MAP3K1 that shows cross-specificity with [[MAP2K1]] <ref>https://www.ncbi.nlm.nih.gov/pubmed/19684251</ref>.


== Interaction partners ==
== Interaction partners ==

Revision as of 17:07, 4 February 2020

MAP3K1
Identifiers
AliasesMAP3K1, MAPKKK1, MEKK, MEKK 1, MEKK1, SRXY6, mitogen-activated protein kinase kinase kinase 1
External IDsOMIM: 600982 MGI: 1346872 HomoloGene: 8056 GeneCards: MAP3K1
Orthologs
SpeciesHumanMouse
Entrez

4214

26401

Ensembl

ENSG00000095015

ENSMUSG00000021754

UniProt

Q13233

P53349

RefSeq (mRNA)

NM_005921

NM_011945

RefSeq (protein)

NP_005912

n/a

Location (UCSC)Chr 5: 56.82 – 56.9 MbChr 13: 111.88 – 111.95 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) is an enzyme that in humans is encoded by the MAP3K1 gene.[5][6]

Function

MAP3K1 (or MEKK1) is a serine/threonine kinase that performs a pivotal role in a network of phosphorylating kinase enzymes integrating cellular receptor responses to a number of mitogenic and metabolic stimuli, including the TNF receptor superfamily (TNFRs), T-cell receptor (TCR), Epidermal growth factor receptor (EGFR), and TGF beta receptor (TGFβR).[7][8] Mitogen-activated protein kinase kinases (MAP2Ks) are substrates for direct phosphorylation by the MAP3K1 protein kinase.[9] Mouse genetics has revealed that MAP3K1 is important in embryonic development, cell growth, cell migration, cytokine production and B cell antibody production.[8] MAP3K1 has been identified by GWAS in breast cancer[10] [11]

Structure

MAP3K1 contains a protein kinase domain as well as PHD finger and scaffold protein regions.[12]

Genetic analyses in murine and avian models

MAP3K1 has been analysed genetically using transgenic mice, embryonic stem cells and the DT40 cell line.[13][14][15][16][17][18][19][20]

Activation and deactivation

Cytokine signaling by MAP3K1 uses a two-stage signaling mechanism.[21][22]

Disease and therapeutic targeting

MAP3K1 is a breast cancer susceptibility allele[23] and 46,XY disorders of sex development gene.[24] E6201 is a chemical inhibitor of MAP3K1 that shows cross-specificity with MAP2K1. [25]

Interaction partners

MAP3K1 has been shown to interact with a number of proteins, including:

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000095015 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021754 – 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. ^ Vinik BS, Kay ES, Fiedorek FT (November 1995). "Mapping of the MEK kinase gene (Mekk) to mouse chromosome 13 and human chromosome 5". Mammalian Genome. 6 (11): 782–3. doi:10.1007/BF00539003. PMID 8597633.
  6. ^ "Entrez Gene: MAP3K1 mitogen-activated protein kinase kinase kinase 1".
  7. ^ Schlesinger TK, Fanger GR, Yujiri T, Johnson GL (November 1998). "The TAO of MEKK". Frontiers in Bioscience : a Journal and Virtual Library. 3: D1181–6. doi:10.2741/a354. PMID 9820741.
  8. ^ a b Suddason T, Gallagher E (April 2015). "A RING to rule them all? Insights into the Map3k1 PHD motif provide a new mechanistic understanding into the diverse roles of Map3k1". Cell Death and Differentiation. 22 (4): 540–8. doi:10.1038/cdd.2014.239. PMC 4356348. PMID 25613373.
  9. ^ Minden A, Lin A, McMahon M, Lange-Carter C, Dérijard B, Davis RJ, Johnson GL, Karin M (December 1994). "Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK". Science. 266 (5191). New York, N.Y.: 1719–23. Bibcode:1994Sci...266.1719M. doi:10.1126/science.7992057. PMID 7992057.
  10. ^ Glubb DM, Maranian MJ, Michailidou K, Pooley KA, Meyer KB, Kar S, et al. (January 2015). "Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1". American Journal of Human Genetics. 96 (1): 5–20. doi:10.1016/j.ajhg.2014.11.009. PMC 4289692. PMID 25529635.
  11. ^ Easton DF, Pooley KA, Dunning AM, Pharoah PD, Thompson D, Ballinger DG, et al. (June 2007). "Genome-wide association study identifies novel breast cancer susceptibility loci". Nature. 447 (7148): 1087–93. Bibcode:2007Natur.447.1087E. doi:10.1038/nature05887. PMC 2714974. PMID 17529967.
  12. ^ "Q13233 (M3K1_HUMAN)". Swiss Model. Swiss Institute of Bioinformatics.
  13. ^ Yujiri T, Sather S, Fanger GR, Johnson GL (December 1998). "Role of MEKK1 in cell survival and activation of JNK and ERK pathways defined by targeted gene disruption". Science. 282 (5395): 1911–4. doi:10.1126/science.282.5395.1911. PMID 9836645.
  14. ^ Yujiri T, Ware M, Widmann C, Oyer R, Russell D, Chan E, et al. (June 2000). "MEK kinase 1 gene disruption alters cell migration and c-Jun NH2-terminal kinase regulation but does not cause a measurable defect in NF-kappa B activation". Proceedings of the National Academy of Sciences of the United States of America. 97 (13): 7272–7. doi:10.1073/pnas.130176697. PMID 10852963.
  15. ^ Zhang L, Wang W, Hayashi Y, Jester JV, Birk DE, Gao M, et al. (September 2003). "A role for MEK kinase 1 in TGF-beta/activin-induced epithelium movement and embryonic eyelid closure". The EMBO Journal. 22 (17): 4443–54. doi:10.1093/emboj/cdg440. PMID 12941696.
  16. ^ Gao M, Labuda T, Xia Y, Gallagher E, Fang D, Liu YC, Karin M (October 2004). "Jun turnover is controlled through JNK-dependent phosphorylation of the E3 ligase Itch". Science. 306 (5694): 271–5. doi:10.1126/science.1099414. PMID 15358865.
  17. ^ Gallagher E, Enzler T, Matsuzawa A, Anzelon-Mills A, Otero D, Holzer R, et al. (January 2007). "Kinase MEKK1 is required for CD40-dependent activation of the kinases Jnk and p38, germinal center formation, B cell proliferation and antibody production". Nature Immunology. 8 (1): 57–63. doi:10.1038/ni1421. PMID 17143273.
  18. ^ Charlaftis N, Suddason T, Wu X, Anwar S, Karin M, Gallagher E (November 2014). "The MEKK1 PHD ubiquitinates TAB1 to activate MAPKs in response to cytokines". The EMBO Journal. 33 (21): 2581–96. doi:10.15252/embj.201488351. PMID 25260751.
  19. ^ Suddason T, Anwar S, Charlaftis N, Gallagher E (January 2016). "T-Cell-Specific Deletion of Map3k1 Reveals the Critical Role for Mekk1 and Jnks in Cdkn1b-Dependent Proliferative Expansion". Cell Reports. 14 (3): 449–457. doi:10.1016/j.celrep.2015.12.047. PMID 26774476.
  20. ^ Kwan R, Burnside J, Kurosaki T, Cheng G (November 2001). "MEKK1 is essential for DT40 cell apoptosis in response to microtubule disruption". Molecular and Cellular Biology. 21 (21): 7183–90. doi:10.1128/MCB.21.21.7183-7190.2001. PMID 11585901.
  21. ^ Matsuzawa A, Tseng PH, Vallabhapurapu S, Luo JL, Zhang W, Wang H, Vignali DA, Gallagher E, Karin M (August 2008). "Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex". Science (New York, N.Y.). 321 (5889): 663–8. doi:10.1126/science.1157340. PMC 2669719. PMID 18635759.
  22. ^ Karin M, Gallagher E (March 2009). "TNFR signaling: ubiquitin-conjugated TRAFfic signals control stop-and-go for MAPK signaling complexes". Immunological Reviews. 228 (1): 225–40. doi:10.1111/j.1600-065X.2008.00755.x. PMID 19290931.
  23. ^ Stephens PJ, Tarpey PS, Davies H, Van Loo P, Greenman C, Wedge DC, et al. (May 2012). "The landscape of cancer genes and mutational processes in breast cancer". Nature. 486 (7403): 400–4. doi:10.1038/nature11017. PMC 3428862. PMID 22722201.
  24. ^ Pearlman A, Loke J, Le Caignec C, White S, Chin L, Friedman A, et al. (December 2010). "Mutations in MAP3K1 cause 46,XY disorders of sex development and implicate a common signal transduction pathway in human testis determination". American Journal of Human Genetics. 87 (6): 898–904. doi:10.1016/j.ajhg.2010.11.003. PMC 2997363. PMID 21129722.
  25. ^ Goto M, Chow J, Muramoto K, Chiba K, Yamamoto S, Fujita M, et al. (November 2009). "E6201 [(3S,4R,5Z,8S,9S,11E)-14-(ethylamino)-8, 9,16-trihydroxy-3,4-dimethyl-3,4,9,19-tetrahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione], a novel kinase inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-1 and MEK kinase-1: in vitro characterization of its anti-inflammatory and antihyperproliferative activities". The Journal of Pharmacology and Experimental Therapeutics. 331 (2): 485–95. doi:10.1124/jpet.109.156554. PMID 19684251.
  26. ^ Zhang Y, Qiu WJ, Chan SC, Han J, He X, Lin SC (May 2002). "Casein kinase I and casein kinase II differentially regulate axin function in Wnt and JNK pathways". The Journal of Biological Chemistry. 277 (20): 17706–12. doi:10.1074/jbc.M111982200. PMID 11884395.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  27. ^ Zhang Y, Neo SY, Han J, Lin SC (August 2000). "Dimerization choices control the ability of axin and dishevelled to activate c-Jun N-terminal kinase/stress-activated protein kinase". The Journal of Biological Chemistry. 275 (32): 25008–14. doi:10.1074/jbc.M002491200. PMID 10829020.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  28. ^ a b c Karandikar M, Xu S, Cobb MH (December 2000). "MEKK1 binds raf-1 and the ERK2 cascade components". The Journal of Biological Chemistry. 275 (51): 40120–7. doi:10.1074/jbc.M005926200. PMID 10969079.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  29. ^ Pomérance M, Multon MC, Parker F, Venot C, Blondeau JP, Tocqué B, Schweighoffer F (September 1998). "Grb2 interaction with MEK-kinase 1 is involved in regulation of Jun-kinase activities in response to epidermal growth factor". The Journal of Biological Chemistry. 273 (38): 24301–4. doi:10.1074/jbc.273.38.24301. PMID 9733714.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  30. ^ Xu S, Cobb MH (December 1997). "MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases". The Journal of Biological Chemistry. 272 (51): 32056–60. doi:10.1074/jbc.272.51.32056. PMID 9405400.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  31. ^ Baud V, Liu ZG, Bennett B, Suzuki N, Xia Y, Karin M (May 1999). "Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain". Genes & Development. 13 (10): 1297–308. doi:10.1101/gad.13.10.1297. PMC 316725. PMID 10346818.
  32. ^ Saltzman A, Searfoss G, Marcireau C, Stone M, Ressner R, Munro R, Franks C, D'Alonzo J, Tocque B, Jaye M, Ivashchenko Y (April 1998). "hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity". FEBS Letters. 425 (3): 431–5. doi:10.1016/s0014-5793(98)00287-7. PMID 9563508.
  33. ^ https://www.ncbi.nlm.nih.gov/pubmed/25260751
  34. ^ https://www.ncbi.nlm.nih.gov/pubmed/14581471
  35. ^ https://www.ncbi.nlm.nih.gov/pubmed/9305638
  36. ^ https://www.ncbi.nlm.nih.gov/pubmed/12115726


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