A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3

Tetsuo Moriguchi, Noriyo Kuroyanagi, Kyoko Yamaguchi, Yukiko Gotoh, Kenji Irie, Takahisa Kano, Kyoko Shirakabe, Yoshinao Muro, Hiroshi Shibuya, Kunihiro Matsumoto, Eisuke Nishida, Masatoshi Hagiwara

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A cDNA encoding a novel member of the mitogen-activated protein kinase kinase (MAPKK) family, MAPKK6, was isolated and found to encode a protein of 334 amine acids, with a calculated molecular mass of 37 kDa that is 79% identical to MKK3. MAPKK6 was shown to phosphorylate and specifically activate the p38/MPK2 subgroup of the mitogen-activated protein kinase superfamily and could be demonstrated to be phosphorylated and activated in vitro by TAK1, a recently identified MAPKK kinase. MKK3 was also shown to be a good substrate for TAK1 in vitro. Furthermore, when co-expressed with TAK1 in cells in culture, both MAPKK6 and MKK3 were strongly activated. In addition, co-expression of TAK1 and p38/MPK2 in cells resulted in activation of p38/MPK2. These results indicate the existence of a novel kinase cascade consisting of TAK1, MAPKK6/MKK3, and p38/MPK2.

Original languageEnglish
Pages (from-to)13675-13679
Number of pages5
JournalJournal of Biological Chemistry
Issue number23
Publication statusPublished - 1996


ASJC Scopus subject areas

  • Biochemistry

Cite this

Moriguchi, T., Kuroyanagi, N., Yamaguchi, K., Gotoh, Y., Irie, K., Kano, T., Shirakabe, K., Muro, Y., Shibuya, H., Matsumoto, K., Nishida, E., & Hagiwara, M. (1996). A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3. Journal of Biological Chemistry, 271(23), 13675-13679. https://doi.org/10.1074/jbc.271.23.13675