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MAP3K1
Identifiers
Aliases	MAP3K1, MAPKKK1, MEKK, MEKK 1, MEKK1, SRXY6, mitogen-activated protein kinase kinase kinase 1
External IDs	OMIM: 600982; MGI: 1346872; HomoloGene: 8056; GeneCards: MAP3K1; OMA:MAP3K1 - orthologs
Gene location (Human) Chr. Chromosome 5 (human) Band 5q11.2 Start 56,815,549 bp End 56,896,152 bp
Gene location (Mouse) Chr. Chromosome 13 (mouse) Band 13 D2.2|13 63.36 cM Start 111,882,962 bp End 111,945,527 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in buccal mucosa cell skin of thigh skin of hip parotid gland corpus epididymis monocyte vulva oral cavity lactiferous duct gums Top expressed in corneal stroma submandibular gland lactiferous gland parotid gland cumulus cell blood epithelium of stomach neural layer of retina Ileal epithelium spleen More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding zinc ion binding metal ion binding kinase activity protein binding MAP kinase kinase kinase activity ATP binding protein kinase binding protein kinase activity protein serine/threonine kinase activity Cellular component cytoplasm cytosol Biological process phosphorylation MyD88-dependent toll-like receptor signaling pathway Fc-epsilon receptor signaling pathway protein phosphorylation cellular response to mechanical stimulus MAPK cascade regulation of mitotic cell cycle signal transduction stress-activated protein kinase signaling cascade activation of protein kinase activity regulation of apoptotic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 13: 111.88 – 111.95 Mb PubMed search
Wikidata
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Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) is a signal transduction enzyme that in humans is encoded by the autosomal MAP3K1 gene.

Function

MAP3K1 (or MEKK1) is a serine/threonine kinase and ubiquitin ligase that performs a pivotal role in a network of enzymes integrating cellular receptor responses to a number of mitogenic and metabolic stimuli, including: TNF receptor superfamily (TNFRs), T-cell receptor (TCR), Epidermal growth factor receptor (EGFR), and TGF beta receptor (TGFβR). Mitogen-activated protein kinase kinases (MAP2Ks) are substrates for direct phosphorylation by the MAP3K1 protein kinase. The MAP3K1 kinase domain may also be a modest activator of IκB kinase activation. The MAP3K1 E3 ubiquitin ligase recruits a ubiquitin-conjugating enzyme (including UBE2D2, UBE2D3, and UBE2N:UBE2V1) that has been loaded with ubiquitin, interacts with its substrates, and facilitates the transfer of ubiquitin from the ubiquitin-conjugating enzyme onto its substrates. Genetics has revealed that MAP3K1 is important in: embryonic development, tumorigenesis, cell growth, cell migration, cytokine production, and humoral immunity. MAP3K1 mutants were identified in breast cancer by GWAS.

Structure

MAP3K1 contains a protein kinase domain, PHD finger (which has a RING finger domain-like structure) that serves as an E3 ubiquitin ligase, and scaffold protein regions that mediate protein–protein interactions.

Genetic analyses in murine and avian models

MAP3K1 is highly conserved in Euteleostomi. The spontaneous recessive lidgap-Gates mutation (deletion of Map3k1 exons 2–9, initially described in the 1960s) identified on the SELH/Bc mouse strain causes the same open-eyelids-at-birth mutational phenotype as the gene knockout mutations of the mouse (but not human) MAP3K1 homolog (Map3k1) and also co-maps to distal Chromosome 13. MAP3K1 was analysed genetically by targeted mutagenesis using transgenic mice (C57BL/6 and C57BL/6 × 129 backgrounds), embryonic stem cells, and the DT40 cell line to identify genetic traits.

Mechanism of MAPK activation by MAP3K1

MAP3K1 contains multiple amino acid sites that are phosphorylated and ubiquitinated. Early biochemical analysis demonstrated that triple co-expression of MAP3K1, MAP2K and MAPK in bacterial cells was sufficient for the activation of MAPK. Later analysis of syngenic mice that harbour mutations in TRAF2, UBE2N, Map3k1 and Map3k7 identified critical regulators of cytokine-induced MAPK signal transduction in B cells. Cytokine signaling through MAP3K1 utilises two-stage cell signaling to recruit the signal transduction mechanism to cytokine receptors and then release the signal transduction components, altered by post-translational modification, from the cellular membrane to activate MAPKs. Genetic analysis has demonstrated that the E3 Ub ligase  and the kinase domains of MAP3K1 are required for MAPK activation.

Cancers, other diseases and therapeutic targeting

MAP3K1 is a biomarker mutated in 3.24% of all human cancers. MAP3K1 has been associated with several diseases in non-syngeneic human populations, including: breast cancer, adenocarcinoma of the prostate, sarcomatoid hepatocellular carcinoma, acute respiratory distress syndrome, Langerhans cell histiocytosis, and 46,XY disorders of sex development. E6201 is an enzyme inhibitor of MAP3K1 that shows cross-specificity with MAP2K1.

Interaction partners

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

• AXIN1,
• C-Raf, MAP2K1, MAPK1,
• Grb2,
• MAPK8,
• TRAF2,
• UBE2I.
• TAB1, TNIP1, TNIP2. Signal transducing adaptor molecule,
• Transforming protein RhoA,
• RAC1, CDC42,
• ARHGAP4,
• MAP2K4, and
• PTK2.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000095015 – Ensembl, May 2017
2. ^ 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): 782–783. doi:10.1007/BF00539003. PMID 8597633. S2CID 37828255.
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. 3 (4): D1181–D1186. doi:10.2741/a354. PMID 9820741.
8. ^ 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): 540–548. doi:10.1038/cdd.2014.239. PMC 4356348. PMID 25613373.
9. Minden A, Lin A, McMahon M, Lange-Carter C, Dérijard B, Davis RJ, et al. (December 1994). "Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK". Science. 266 (5191): 1719–1723. Bibcode:1994Sci...266.1719M. doi:10.1126/science.7992057. PMID 7992057.
10. Karin M, Gallagher E (2005). "From JNK to pay dirt: jun kinases, their biochemistry, physiology and clinical importance". IUBMB Life. 57 (4–5): 283–295. doi:10.1080/15216540500097111. PMID 16036612. S2CID 25508987.
11. Karin M, Delhase M (August 1998). "JNK or IKK, AP-1 or NF-kappaB, which are the targets for MEK kinase 1 action?". Proceedings of the National Academy of Sciences of the United States of America. 95 (16): 9067–9069. Bibcode:1998PNAS...95.9067K. doi:10.1073/pnas.95.16.9067. PMC 33875. PMID 9689033.
12. ^ 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): 2581–2596. doi:10.15252/embj.201488351. PMC 4282369. PMID 25260751.
13. 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.
14. 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): 1087–1093. Bibcode:2007Natur.447.1087E. doi:10.1038/nature05887. PMC 2714974. PMID 17529967.
15. "Q13233 (M3K1_HUMAN)". Swiss Model. Swiss Institute of Bioinformatics.
16. Yan M, Dai T, Deak JC, Kyriakis JM, Zon LI, Woodgett JR, Templeton DJ (22–29 December 1994). "Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1". Nature. 372 (6508): 798–800. Bibcode:1994Natur.372..798Y. doi:10.1038/372798a0. PMID 7997270. S2CID 4369739.
17. Lu Z, Xu S, Joazeiro C, Cobb MH, Hunter T (May 2002). "The PHD domain of MEKK1 acts as an E3 ubiquitin ligase and mediates ubiquitination and degradation of ERK1/2". Molecular Cell. 9 (5): 945–956. doi:10.1016/s1097-2765(02)00519-1. PMID 12049732.
18. Filipčík P, Latham SL, Cadell AL, Day CL, Croucher DR, Mace PD (September 2020). "A cryptic tubulin-binding domain links MEKK1 to curved tubulin protomers". Proceedings of the National Academy of Sciences of the United States of America. 117 (35): 21308–21318. Bibcode:2020PNAS..11721308F. doi:10.1073/pnas.2006429117. PMC 7474687. PMID 32817551.
19. "HomoloGene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-05-01.
20. Juriloff DM, Harris MJ, Mah DG (January 2005). "The open-eyelid mutation, lidgap-Gates, is an eight-exon deletion in the mouse Map3k1 gene". Genomics. 85 (1): 139–142. doi:10.1016/j.ygeno.2004.10.002. PMID 15607429.
21. 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): 1911–1914. Bibcode:1998Sci...282.1911Y. doi:10.1126/science.282.5395.1911. PMID 9836645.
22. 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): 7272–7277. Bibcode:2000PNAS...97.7272Y. doi:10.1073/pnas.130176697. PMC 16535. PMID 10852963.
23. Yujiri T, Fanger GR, Garrington TP, Schlesinger TK, Gibson S, Johnson GL (April 1999). "MEK kinase 1 (MEKK1) transduces c-Jun NH2-terminal kinase activation in response to changes in the microtubule cytoskeleton". The Journal of Biological Chemistry. 274 (18): 12605–12610. doi:10.1074/jbc.274.18.12605. PMID 10212239. S2CID 37158636.
24. Minamino T, Yujiri T, Papst PJ, Chan ED, Johnson GL, Terada N (December 1999). "MEKK1 suppresses oxidative stress-induced apoptosis of embryonic stem cell-derived cardiac myocytes". Proceedings of the National Academy of Sciences of the United States of America. 96 (26): 15127–15132. Bibcode:1999PNAS...9615127M. doi:10.1073/pnas.96.26.15127. PMC 24784. PMID 10611349.
25. 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): 4443–4454. doi:10.1093/emboj/cdg440. PMC 202382. PMID 12941696.
26. 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): 271–275. Bibcode:2004Sci...306..271G. doi:10.1126/science.1099414. PMID 15358865. S2CID 31876966.
27. 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. S2CID 23344995.
28. Bonnesen B, Orskov C, Rasmussen S, Holst PJ, Christensen JP, Eriksen KW, et al. (November 2005). "MEK kinase 1 activity is required for definitive erythropoiesis in the mouse fetal liver". Blood. 106 (10): 3396–3404. doi:10.1182/blood-2005-04-1739. PMID 16081685. S2CID 19307521.
29. Labuda T, Christensen JP, Rasmussen S, Bonnesen B, Karin M, Thomsen AR, Odum N (August 2006). "MEK kinase 1 is a negative regulator of virus-specific CD8(+) T cells". European Journal of Immunology. 36 (8): 2076–2084. doi:10.1002/eji.200535163. PMID 16761309. S2CID 12332084.
30. 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. PMC 4733086. PMID 26774476.
31. 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): 7183–7190. doi:10.1128/MCB.21.21.7183-7190.2001. PMC 99893. PMID 11585901.
32. ^ Tricker E, Arvand A, Kwan R, Chen GY, Gallagher E, Cheng G (February 2011). "Apoptosis induced by cytoskeletal disruption requires distinct domains of MEKK1". PLOS ONE. 6 (2): e17310. Bibcode:2011PLoSO...617310T. doi:10.1371/journal.pone.0017310. PMC 3045432. PMID 21364884.
33. "MEKK1 (human)". www.phosphosite.org. Retrieved 2020-02-26.
34. Khokhlatchev A, Xu S, English J, Wu P, Schaefer E, Cobb MH (April 1997). "Reconstitution of mitogen-activated protein kinase phosphorylation cascades in bacteria. Efficient synthesis of active protein kinases". The Journal of Biological Chemistry. 272 (17): 11057–11062. doi:10.1074/jbc.272.17.11057. PMID 9110999.
35. Lee SY, Reichlin A, Santana A, Sokol KA, Nussenzweig MC, Choi Y (November 1997). "TRAF2 is essential for JNK but not NF-kappaB activation and regulates lymphocyte proliferation and survival". Immunity. 7 (5): 703–713. doi:10.1016/s1074-7613(00)80390-8. PMID 9390693.
36. Yamamoto M, Okamoto T, Takeda K, Sato S, Sanjo H, Uematsu S, et al. (September 2006). "Key function for the Ubc13 E2 ubiquitin-conjugating enzyme in immune receptor signaling". Nature Immunology. 7 (9): 962–970. doi:10.1038/ni1367. PMID 16862162. S2CID 34181754.
37. Sato S, Sanjo H, Takeda K, Ninomiya-Tsuji J, Yamamoto M, Kawai T, et al. (November 2005). "Essential function for the kinase TAK1 in innate and adaptive immune responses". Nature Immunology. 6 (11): 1087–1095. doi:10.1038/ni1255. PMID 16186825. S2CID 13005309.
38. 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. S2CID 23344995.
39. Matsuzawa A, Tseng PH, Vallabhapurapu S, Luo JL, Zhang W, Wang H, et al. (August 2008). "Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex". Science. 321 (5889): 663–668. Bibcode:2008Sci...321..663M. doi:10.1126/science.1157340. PMC 2669719. PMID 18635759.
40. Karin M, Gallagher E (March 2009). "TNFR signaling: ubiquitin-conjugated TRAFfic signals control stop-and-go for MAPK signaling complexes". Immunological Reviews. 228 (1): 225–240. doi:10.1111/j.1600-065X.2008.00755.x. PMID 19290931. S2CID 1683105.
41. ^ 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): 2581–2596. doi:10.15252/embj.201488351. PMC 4282369. PMID 25260751.
42. Xia Y, Makris C, Su B, Li E, Yang J, Nemerow GR, Karin M (May 2000). "MEK kinase 1 is critically required for c-Jun N-terminal kinase activation by proinflammatory stimuli and growth factor-induced cell migration". Proceedings of the National Academy of Sciences of the United States of America. 97 (10): 5243–5248. Bibcode:2000PNAS...97.5243X. doi:10.1073/pnas.97.10.5243. PMC 25813. PMID 10805784.
43. "MAP3K1 - My Cancer Genome". www.mycancergenome.org. Retrieved 2020-02-26.
44. ^ "MAP3K1 mitogen-activated protein kinase kinase kinase 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-05-02.
45. 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): 400–404. Bibcode:2012Natur.486..400.. doi:10.1038/nature11017. PMC 3428862. PMID 22722201.
46. Shojo K, Kosaka T, Nakamura K, Hongo H, Kobayashi H, Mikami S, et al. (May 2021). "First case of ductal adenocarcinoma of the prostate with MAP3K1 homozygous deletion". IJU Case Reports. 4 (3): 176–179. doi:10.1002/iju5.12274. PMC 8088887. PMID 33977253.
47. Zhang C, Feng S, Tu Z, Sun J, Rui T, Zhang X, et al. (September 2021). "Sarcomatoid hepatocellular carcinoma: From clinical features to cancer genome". Cancer Medicine. 10 (18): 6227–6238. doi:10.1002/cam4.4162. PMC 8446410. PMID 34331411.
48. Morrell ED, O'Mahony DS, Glavan BJ, Harju-Baker S, Nguyen C, Gunderson S, et al. (January 2018). "Genetic Variation in MAP3K1 Associates with Ventilator-Free Days in Acute Respiratory Distress Syndrome". American Journal of Respiratory Cell and Molecular Biology. 58 (1): 117–125. doi:10.1165/rcmb.2017-0030OC. PMC 5941309. PMID 28858533.
49. Nelson DS, van Halteren A, Quispel WT, van den Bos C, Bovée JV, Patel B, et al. (June 2015). "MAP2K1 and MAP3K1 mutations in Langerhans cell histiocytosis". Genes, Chromosomes & Cancer. 54 (6): 361–368. doi:10.1002/gcc.22247. PMID 25899310. S2CID 6264217.
50. 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.
51. Goto M, Chow J, Muramoto K, Chiba K, Yamamoto S, Fujita M, et al. (November 2009). "E6201 , 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): 485–495. doi:10.1124/jpet.109.156554. PMID 19684251. S2CID 37755563.
52. 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): 17706–17712. doi:10.1074/jbc.M111982200. PMID 11884395.
53. 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): 25008–25014. doi:10.1074/jbc.M002491200. PMID 10829020.
54. Karandikar M, Xu S, Cobb MH (December 2000). "MEKK1 binds raf-1 and the ERK2 cascade components". The Journal of Biological Chemistry. 275 (51): 40120–40127. doi:10.1074/jbc.M005926200. PMID 10969079.
55. 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): 24301–24304. doi:10.1074/jbc.273.38.24301. PMID 9733714.
56. 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): 32056–32060. doi:10.1074/jbc.272.51.32056. PMID 9405400.
57. 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): 1297–1308. doi:10.1101/gad.13.10.1297. PMC 316725. PMID 10346818.
58. Saltzman A, Searfoss G, Marcireau C, Stone M, Ressner R, Munro R, et al. (April 1998). "hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity". FEBS Letters. 425 (3): 431–435. Bibcode:1998FEBSL.425..431S. doi:10.1016/s0014-5793(98)00287-7. PMID 9563508. S2CID 84816080.
59. Gallagher ED, Gutowski S, Sternweis PC, Cobb MH (January 2004). "RhoA binds to the amino terminus of MEKK1 and regulates its kinase activity". The Journal of Biological Chemistry. 279 (3): 1872–1877. doi:10.1074/jbc.M309525200. PMID 14581471.
60. Fanger GR, Johnson NL, Johnson GL (August 1997). "MEK kinases are regulated by EGF and selectively interact with Rac/Cdc42". The EMBO Journal. 16 (16): 4961–4972. doi:10.1093/emboj/16.16.4961. PMC 1170131. PMID 9305638.
61. Christerson LB, Gallagher E, Vanderbilt CA, Whitehurst AW, Wells C, Kazempour R, et al. (August 2002). "p115 Rho GTPase activating protein interacts with MEKK1". Journal of Cellular Physiology. 192 (2): 200–208. doi:10.1002/jcp.10125. PMID 12115726. S2CID 33717402.
62. 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): 3369–3381. doi:10.1101/gad.12.21.3369. PMC 317229. PMID 9808624.
63. Yujiri T, Nawata R, Takahashi T, Sato Y, Tanizawa Y, Kitamura T, Oka Y (February 2003). "MEK kinase 1 interacts with focal adhesion kinase and regulates insulin receptor substrate-1 expression". The Journal of Biological Chemistry. 278 (6): 3846–3851. doi:10.1074/jbc.M206087200. PMID 12458213.

Further reading

• Lin, A (2006). "The JNK Signaling Pathway (Molecular Biology Intelligence Unit)". Landes Bioscience. 1: 1–97. ISBN 978-1587061202.

• Biology

• Genes on human chromosome 5
• Mitogen-activated protein kinases
• EC 2.7.11
• Biomarkers