Identification of a Member of the MAPKKK Family as a Potential Mediator of TGF-β Signal Transduction

• DOI: 10.1126/science.270.5244.2008
• Publication Date: 2006-10-27T18:19:42Z
• Authors: Kyoko Yamaguchi; Kyoko Shirakabe; Hiroshi Shibuya; Kenji Irie; Isao Oishi; Naoto Ueno; Tadatsugu Taniguchi; Eisuke Nishida; Kunihiro Matsumoto
• Keywords: 0303 health sciences; Base Sequence; Epidermal Growth Factor; Molecular Sequence Data; Proteins; Saccharomyces cerevisiae; Protein Serine-Threonine Kinases; MAP Kinase Kinase Kinases; Transfection; Cell Line; Mice; 03 medical and health sciences; Gene Expression Regulation; Genes, Reporter; Transforming Growth Factor beta; Bone Morphogenetic Proteins; Animals; Amino Acid Sequence; Cloning, Molecular; Signal Transduction

The mitogen-activated protein kinase (MAPK) pathway is a conserved eukaryotic signaling module that converts receptor signals into various outputs. MAPK is activated through phosphorylation by MAPK kinase (MAPKK), which is first activated by MAPKK kinase (MAPKKK). A genetic selection based on a MAPK pathway in yeast was used to identify a mouse protein kinase (TAK1) distinct from other members of the MAPKKK family. TAK1 was shown to participate in regulation of transcription by transforming growth factor-β (TGF-β). Furthermore, kinase activity of TAK1 was stimulated in response to TGF-β and bone morphogenetic protein. These results suggest that TAK1 functions as a mediator in the signaling pathway of TGF-β superfamily members.