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Gene Review

Map3k10  -  mitogen-activated protein kinase kinase...

Mus musculus

Synonyms: BC028668, BC046514, MKN28 derived nonreceptor_type, MKN28 kinase, MST, ...
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Disease relevance of Map3k10


High impact information on Map3k10


Chemical compound and disease context of Map3k10

  • The treatment of Swiss mice with himachalol (200 mg kg-1, po) once a day, for 7 days, provided 60% protection concomitantly with increased MST (15 days) against invasive aspergillosis [11].

Biological context of Map3k10


Anatomical context of Map3k10

  • Expression of mixed lineage kinase 2 in germ cells of the testis [16].
  • Sequence analysis of v-akt and biochemical characterization of its product revealed that it codes for a protein kinase C-related serine-threonine kinase whose cellular homolog is expressed in most tissues, with the highest amount found in thymus [12].
  • Here we report that the serine-threonine kinase MINK selectively connects the T cell receptor to a signaling pathway that mediates negative but not positive selection [17].
  • The serine-threonine kinase Raf protein is phosphorylation-activated by a large array of agonists including plasma membrane and cytoplasmic tyrosine kinases but has not previously been associated with the steroid superfamily of mediators [18].
  • Mice in this group rejected their grafts acutely (MST 12 days), suggesting indeed that stem cells might be very important in the success of this model [19].

Associations of Map3k10 with chemical compounds

  • Here we show that the serine-threonine kinase protein kinase C epsilon (PKCepsilon) functions as a signal integrator between cytokine and integrin signalling pathways [20].
  • In the liver, insulin controls both lipid and glucose metabolism through its cell surface receptor and intracellular mediators such as phosphatidylinositol 3-kinase and serine-threonine kinase AKT [21].
  • Deaminative cleavage of MST heparin by HNO2 at pH 1.5 released disaccharides that were similar in composition to those obtained from commercial heparin, except that disaccharides containing 3,6-O-desulfated GlcN units were not found [22].
  • During mitosis, PLK is phosphorylated on serine, and its serine threonine kinase function is activated at a time close to that of p34cdc2 [23].
  • Treatment of donor, hand-picked islets with a mixture of cross-reactive anti-Ia antibodies and complement without cyclosporin-A therapy did not prolong the survival of islet allografts (MST, 6.5 +/- 0.4 days versus 7.0 +/- 0.5 days in controls) [24].

Enzymatic interactions of Map3k10


Regulatory relationships of Map3k10


Other interactions of Map3k10


Analytical, diagnostic and therapeutic context of Map3k10

  • Members of the TGF-beta superfamily of signalling molecules work by activating transmembrane receptors with phosphorylating activity (serine-threonine kinase receptors); these in turn phosphorylate and activate SMADs, a class of signal transducers [34].
  • In wild-type cells, we found CARD9 inducibly associated with both the intracellular 'biosensor' Nod2 and the serine-threonine kinase RICK [35].
  • The control group had MST of 7.3 days [36].
  • As with fully xenogeneic chimeras (rat-->mouse), synchronous donor-specific F344 rat (Rt1A1) islet xenografts were significantly prolonged (MST > 139 days) in mixed xenogeneic (mouse+rat-->mouse) chimeras, while MHC-disparate third-party WF rat (Rt1Au) grafts were rejected (MST = 21.2 days) [37].
  • However, when the primary heart graft was removed 50 days after transplantation, a time point when tolerance to donor alloantigens was demonstrable in vivo, tolerance was lost 200 days later (MST of second C57 heart grafts 31 days) [38].


  1. WNK4 regulates the balance between renal NaCl reabsorption and K+ secretion. Kahle, K.T., Wilson, F.H., Leng, Q., Lalioti, M.D., O'Connell, A.D., Dong, K., Rapson, A.K., MacGregor, G.G., Giebisch, G., Hebert, S.C., Lifton, R.P. Nat. Genet. (2003) [Pubmed]
  2. PI3K rescues the detrimental effects of chronic Akt activation in the heart during ischemia/reperfusion injury. Nagoshi, T., Matsui, T., Aoyama, T., Leri, A., Anversa, P., Li, L., Ogawa, W., del Monte, F., Gwathmey, J.K., Grazette, L., Hemmings, B.A., Hemmings, B., Kass, D.A., Champion, H.C., Rosenzweig, A. J. Clin. Invest. (2005) [Pubmed]
  3. Antitumor activity of combined blockade of epidermal growth factor receptor and protein kinase A. Ciardiello, F., Damiano, V., Bianco, R., Bianco, C., Fontanini, G., De Laurentiis, M., De Placido, S., Mendelsohn, J., Bianco, A.R., Tortora, G. J. Natl. Cancer Inst. (1996) [Pubmed]
  4. WNK4 regulates apical and basolateral Cl- flux in extrarenal epithelia. Kahle, K.T., Gimenez, I., Hassan, H., Wilson, F.H., Wong, R.D., Forbush, B., Aronson, P.S., Lifton, R.P. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  5. Overexpression of the Tpl-2/Cot oncogene in human breast cancer. Sourvinos, G., Tsatsanis, C., Spandidos, D.A. Oncogene (1999) [Pubmed]
  6. Globozoospermia in mice lacking the casein kinase II alpha' catalytic subunit. Xu, X., Toselli, P.A., Russell, L.D., Seldin, D.C. Nat. Genet. (1999) [Pubmed]
  7. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Datta, S.R., Dudek, H., Tao, X., Masters, S., Fu, H., Gotoh, Y., Greenberg, M.E. Cell (1997) [Pubmed]
  8. A crucial role for GRK2 in regulation of endothelial cell nitric oxide synthase function in portal hypertension. Liu, S., Premont, R.T., Kontos, C.D., Zhu, S., Rockey, D.C. Nat. Med. (2005) [Pubmed]
  9. Identification of a putative target for Rho as the serine-threonine kinase protein kinase N. Amano, M., Mukai, H., Ono, Y., Chihara, K., Matsui, T., Hamajima, Y., Okawa, K., Iwamatsu, A., Kaibuchi, K. Science (1996) [Pubmed]
  10. Premature p34cdc2 activation required for apoptosis. Shi, L., Nishioka, W.K., Th'ng, J., Bradbury, E.M., Litchfield, D.W., Greenberg, A.H. Science (1994) [Pubmed]
  11. Comparative in vitro and in vivo evaluation of himachalol in murine invasive aspergillosis. Chowdhry, L., Khan, Z.K., Kulshrestha, D.K. Indian J. Exp. Biol. (1997) [Pubmed]
  12. A retroviral oncogene, akt, encoding a serine-threonine kinase containing an SH2-like region. Bellacosa, A., Testa, J.R., Staal, S.P., Tsichlis, P.N. Science (1991) [Pubmed]
  13. Activated Akt protects the lung from oxidant-induced injury and delays death of mice. Lu, Y., Parkyn, L., Otterbein, L.E., Kureishi, Y., Walsh, K., Ray, A., Ray, P. J. Exp. Med. (2001) [Pubmed]
  14. The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2. Berg, J.N., Gallione, C.J., Stenzel, T.T., Johnson, D.W., Allen, W.P., Schwartz, C.E., Jackson, C.E., Porteous, M.E., Marchuk, D.A. Am. J. Hum. Genet. (1997) [Pubmed]
  15. Insulin hypersensitivity and resistance to streptozotocin-induced diabetes in mice lacking PTEN in adipose tissue. Kurlawalla-Martinez, C., Stiles, B., Wang, Y., Devaskar, S.U., Kahn, B.B., Wu, H. Mol. Cell. Biol. (2005) [Pubmed]
  16. Expression of mixed lineage kinase 2 in germ cells of the testis. Phelan, D.R., Loveland, K.L., Devereux, L., Dorow, D.S. Mol. Reprod. Dev. (1999) [Pubmed]
  17. Signaling by the kinase MINK is essential in the negative selection of autoreactive thymocytes. McCarty, N., Paust, S., Ikizawa, K., Dan, I., Li, X., Cantor, H. Nat. Immunol. (2005) [Pubmed]
  18. 1,25-Dihydroxyvitamin D3 activates Raf kinase and Raf perinuclear translocation via a protein kinase C-dependent pathway. Lissoos, T.W., Beno, D.W., Davis, B.H. J. Biol. Chem. (1993) [Pubmed]
  19. Donor-recipient microchimerism is not required for tolerance induction following recipient pretreatment with donor-specific transfusion and anti-CD4 antibody. Evidence of a clear role for short-term antigen persistence. Bushell, A., Pearson, T.C., Morris, P.J., Wood, K.J. Transplantation (1995) [Pubmed]
  20. PKCepsilon is a permissive link in integrin-dependent IFN-gamma signalling that facilitates JAK phosphorylation of STAT1. Ivaska, J., Bosca, L., Parker, P.J. Nat. Cell Biol. (2003) [Pubmed]
  21. Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity [corrected]. Stiles, B., Wang, Y., Stahl, A., Bassilian, S., Lee, W.P., Kim, Y.J., Sherwin, R., Devaskar, S., Lesche, R., Magnuson, M.A., Wu, H. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  22. Stable heparin-producing cell lines derived from the Furth murine mastocytoma. Montgomery, R.I., Lidholt, K., Flay, N.W., Liang, J., Vertel, B., Lindahl, U., Esko, J.D. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  23. Polo-like kinase is a cell cycle-regulated kinase activated during mitosis. Hamanaka, R., Smith, M.R., O'Connor, P.M., Maloid, S., Mihalic, K., Spivak, J.L., Longo, D.L., Ferris, D.K. J. Biol. Chem. (1995) [Pubmed]
  24. The effect of cyclosporin-A, low-temperature culture, and anti-Ia antibodies on prevention of rejection of rat islet allografts. Terasaka, R., Lacy, P.E., Hauptfeld, V., Bucy, R.P., Davie, J.M. Diabetes (1986) [Pubmed]
  25. Erythropoietin stimulates phosphorylation and activation of GATA-1 via the PI3-kinase/AKT signaling pathway. Zhao, W., Kitidis, C., Fleming, M.D., Lodish, H.F., Ghaffari, S. Blood (2006) [Pubmed]
  26. PKC activation by melatonin modulates vimentin intermediate filament organization in N1E-115 cells. Benítez-King, G. J. Pineal Res. (2000) [Pubmed]
  27. Mouse receptor interacting protein 3 does not contain a caspase-recruiting or a death domain but induces apoptosis and activates NF-kappaB. Pazdernik, N.J., Donner, D.B., Goebl, M.G., Harrington, M.A. Mol. Cell. Biol. (1999) [Pubmed]
  28. Regulation of urokinase-type plasminogen activator expression by the v-mos oncogene. Lengye, E., Singh, B., Gum, R., Nerlov, C., Sabichi, A., Birrer, M., Boyd, D. Oncogene (1995) [Pubmed]
  29. Protein tyrosine kinase 6 negatively regulates growth and promotes enterocyte differentiation in the small intestine. Haegebarth, A., Bie, W., Yang, R., Crawford, S.E., Vasioukhin, V., Fuchs, E., Tyner, A.L. Mol. Cell. Biol. (2006) [Pubmed]
  30. S6k1 is not required for Pten-deficient neuronal hypertrophy. Chalhoub, N., Kozma, S.C., Baker, S.J. Brain Res. (2006) [Pubmed]
  31. Control of cortical neuron migration and layering: cell and non cell-autonomous effects of p35. Hammond, V., Tsai, L.H., Tan, S.S. J. Neurosci. (2004) [Pubmed]
  32. Cloning of a type I TGF-beta receptor and its effect on TGF-beta binding to the type II receptor. Ebner, R., Chen, R.H., Shum, L., Lawler, S., Zioncheck, T.F., Lee, A., Lopez, A.R., Derynck, R. Science (1993) [Pubmed]
  33. Platelet-derived growth factor (PDGF)-dependent association of phospholipase C-gamma with the PDGF receptor signaling complex. Morrison, D.K., Kaplan, D.R., Rhee, S.G., Williams, L.T. Mol. Cell. Biol. (1990) [Pubmed]
  34. Smad4 and FAST-1 in the assembly of activin-responsive factor. Chen, X., Weisberg, E., Fridmacher, V., Watanabe, M., Naco, G., Whitman, M. Nature (1997) [Pubmed]
  35. The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens. Hsu, Y.M., Zhang, Y., You, Y., Wang, D., Li, H., Duramad, O., Qin, X.F., Dong, C., Lin, X. Nat. Immunol. (2007) [Pubmed]
  36. A proteasome inhibitor effectively prevents mouse heart allograft rejection. Luo, H., Wu, Y., Qi, S., Wan, X., Chen, H., Wu, J. Transplantation (2001) [Pubmed]
  37. Mixed xenogeneic chimerism (mouse+rat-->mouse) to induce donor-specific tolerance to sequential or simultaneous islet xenografts. Li, H., Ricordi, C., Demetris, A.J., Kaufman, C.L., Korbanic, C., Hronakes, M.L., Ildstad, S.T. Transplantation (1994) [Pubmed]
  38. Evidence that the continued presence of the organ graft and not peripheral donor microchimerism is essential for maintenance of tolerance to alloantigen in vivo in anti-CD4 treated recipients. Hamano, K., Rawsthorne, M.A., Bushell, A.R., Morris, P.J., Wood, K.J. Transplantation (1996) [Pubmed]
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