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Gene Review

Map3k1  -  mitogen-activated protein kinase kinase...

Mus musculus

Synonyms: MAPK/ERK kinase kinase 1, MAPKKK1, MEK kinase 1, MEKK 1, MEKK1, ...
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Disease relevance of Map3k1


High impact information on Map3k1

  • Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction [5].
  • Our data emphasize that MEKK1 is an essential component of signaling cascades needed for thymus-dependent antigen-induced B cell proliferation and antibody production [6].
  • Mice lacking activity of the kinase MEKK1 ('Map3k1(DeltaKD)' mice) have defective activation of the kinase Jnk and increased production of T helper type 2 cytokines after T cell receptor ligation [6].
  • Kinase MEKK1 is required for CD40-dependent activation of the kinases Jnk and p38, germinal center formation, B cell proliferation and antibody production [6].
  • Fourteen days after banding, Mekk1(-/-) hearts were dilated, and their left ventricular ejection fraction was low [1].

Biological context of Map3k1

  • The lg(Ga) mutation is demonstrated to be a 27.5-kb deletion of exons 2-9 in the Map3k1 gene, the first spontaneous mutant allele described at this locus [7].
  • One of these, the recessive lidgap-Gates (lg(Ga)) mutation, causes the same open-eyelids-at-birth phenotype as the gene knockout mutations of Map3k1 and co-maps to distal Chr 13 [7].
  • Three mutants: S218D, S222D and S218D/S222D in which we substituted the Raf1/MAPKKK-dependent regulatory phosphorylation sites by aspartic acid residues, displayed increased basal activity when expressed in fibroblasts [8].
  • Mapping of the MEK kinase gene (Mekk) to mouse chromosome 13 and human chromosome 5 [9].
  • These findings indicate that the C-terminal domain of these proteins encodes a new protein domain family and suggests that this domain couples these kinases to the SAPK pathway, possibly by interacting with MEKK1 or related kinases [10].

Anatomical context of Map3k1


Associations of Map3k1 with chemical compounds


Other interactions of Map3k1


Analytical, diagnostic and therapeutic context of Map3k1


  1. The MEKK1-JNK pathway plays a protective role in pressure overload but does not mediate cardiac hypertrophy. Sadoshima, J., Montagne, O., Wang, Q., Yang, G., Warden, J., Liu, J., Takagi, G., Karoor, V., Hong, C., Johnson, G.L., Vatner, D.E., Vatner, S.F. J. Clin. Invest. (2002) [Pubmed]
  2. A gene encoding a mitogen-activated protein kinase kinase kinase is induced simultaneously with genes for a mitogen-activated protein kinase and an S6 ribosomal protein kinase by touch, cold, and water stress in Arabidopsis thaliana. Mizoguchi, T., Irie, K., Hirayama, T., Hayashida, N., Yamaguchi-Shinozaki, K., Matsumoto, K., Shinozaki, K. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  3. Activation of (His)6-Raf-1 in vitro by partially purified plasma membranes from v-Ras-transformed and serum-stimulated fibroblasts. Dent, P., Sturgill, T.W. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  4. AKT induces transcriptional activity of PU.1 through phosphorylation-mediated modifications within its transactivation domain. Rieske, P., Pongubala, J.M. J. Biol. Chem. (2001) [Pubmed]
  5. Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction. Yamaguchi, K., Shirakabe, K., Shibuya, H., Irie, K., Oishi, I., Ueno, N., Taniguchi, T., Nishida, E., Matsumoto, K. Science (1995) [Pubmed]
  6. Kinase MEKK1 is required for CD40-dependent activation of the kinases Jnk and p38, germinal center formation, B cell proliferation and antibody production. Gallagher, E., Enzler, T., Matsuzawa, A., Anzelon-Mills, A., Otero, D., Holzer, R., Janssen, E., Gao, M., Karin, M. Nat. Immunol. (2007) [Pubmed]
  7. The open-eyelid mutation, lidgap-Gates, is an eight-exon deletion in the mouse Map3k1 gene. Juriloff, D.M., Harris, M.J., Mah, D.G. Genomics (2005) [Pubmed]
  8. Constitutively active mutants of MAP kinase kinase (MEK1) induce growth factor-relaxation and oncogenicity when expressed in fibroblasts. Brunet, A., Pagès, G., Pouysségur, J. Oncogene (1994) [Pubmed]
  9. Mapping of the MEK kinase gene (Mekk) to mouse chromosome 13 and human chromosome 5. Vinik, B.S., Kay, E.S., Fiedorek, F.T. Mamm. Genome (1995) [Pubmed]
  10. NIK is a new Ste20-related kinase that binds NCK and MEKK1 and activates the SAPK/JNK cascade via a conserved regulatory domain. Su, Y.C., Han, J., Xu, S., Cobb, M., Skolnik, E.Y. EMBO J. (1997) [Pubmed]
  11. Overexpression of mitogen-activated protein kinase kinase kinase reversed cAMP inhibition of NF-kappaB in T cells. Ho, H.Y., Lee, H.H., Lai, M.Z. Eur. J. Immunol. (1997) [Pubmed]
  12. Transgenic mice with cardiac-specific over-expression of MLK7 have increased mortality when exposed to chronic beta-adrenergic stimulation. Christe, M., Jin, N., Wang, X., Gould, K.E., Iversen, P.W., Yu, X., Lorenz, J.N., Kadambi, V., Zuckerman, S.H., Bloem, L.J. J. Mol. Cell. Cardiol. (2004) [Pubmed]
  13. Identification of two essential phosphorylated threonine residues in the catalytic domain of Mekk1. Indirect activation by Pak3 and protein kinase C. Siow, Y.L., Kalmar, G.B., Sanghera, J.S., Tai, G., Oh, S.S., Pelech, S.L. J. Biol. Chem. (1997) [Pubmed]
  14. Identification of a MAP kinase kinase kinase in phaeochromocytoma (PC12) cells. Gomez, N., Traverse, S., Cohen, P. FEBS Lett. (1992) [Pubmed]
  15. Targeted disruption of the MKK4 gene causes embryonic death, inhibition of c-Jun NH2-terminal kinase activation, and defects in AP-1 transcriptional activity. Yang, D., Tournier, C., Wysk, M., Lu, H.T., Xu, J., Davis, R.J., Flavell, R.A. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  16. Zn(2+) induces stimulation of the c-Jun N-terminal kinase signaling pathway through phosphoinositide 3-Kinase. Eom, S.J., Kim, E.Y., Lee, J.E., Kang, H.J., Shim, J., Kim, S.U., Gwag, B.J., Choi, E.J. Mol. Pharmacol. (2001) [Pubmed]
  17. Cisplatin potentiates 1,25-dihydroxyvitamin D3-induced apoptosis in association with increased mitogen-activated protein kinase kinase kinase 1 (MEKK-1) expression. Hershberger, P.A., McGuire, T.F., Yu, W.D., Zuhowski, E.G., Schellens, J.H., Egorin, M.J., Trump, D.L., Johnson, C.S. Mol. Cancer Ther. (2002) [Pubmed]
  18. MEKK1 is essential for cardiac hypertrophy and dysfunction induced by Gq. Minamino, T., Yujiri, T., Terada, N., Taffet, G.E., Michael, L.H., Johnson, G.L., Schneider, M.D. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  19. Activation of MEKK1 by Rho GTPases. Chen, Z., Cobb, M.H. Meth. Enzymol. (2006) [Pubmed]
  20. Apoptosis signal-regulating kinase 1 is involved not only in apoptosis but also in non-apoptotic cardiomyocyte death. Watanabe, T., Otsu, K., Takeda, T., Yamaguchi, O., Hikoso, S., Kashiwase, K., Higuchi, Y., Taniike, M., Nakai, A., Matsumura, Y., Nishida, K., Ichijo, H., Hori, M. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  21. Evidence of an interaction between Mos and Hsp70: a role of the Mos residue serine 3 in mediating Hsp70 association. Liu, H., Vuyyuru, V.B., Pham, C.D., Yang, Y., Singh, B. Oncogene (1999) [Pubmed]
  22. Differential regulation of interleukin 1 receptor and Toll-like receptor signaling by MEKK3. Huang, Q., Yang, J., Lin, Y., Walker, C., Cheng, J., Liu, Z.G., Su, B. Nat. Immunol. (2004) [Pubmed]
  23. The Cryptococcus neoformans STE11alpha gene is similar to other fungal mitogen-activated protein kinase kinase kinase (MAPKKK) genes but is mating type specific. Clarke, D.L., Woodlee, G.L., McClelland, C.M., Seymour, T.S., Wickes, B.L. Mol. Microbiol. (2001) [Pubmed]
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