Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction

Science. 1995 Dec 22;270(5244):2008-11. doi: 10.1126/science.270.5244.2008.


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-beta (TGF-beta). Furthermore, kinase activity of TAK1 was stimulated in response to TGF-beta and bone morphogenetic protein. These results suggest that TAK1 functions as a mediator in the signaling pathway of TGF-beta superfamily members.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Bone Morphogenetic Proteins
  • Cell Line
  • Cloning, Molecular
  • Epidermal Growth Factor / pharmacology
  • Gene Expression Regulation*
  • Genes, Reporter
  • MAP Kinase Kinase Kinases*
  • Mice
  • Molecular Sequence Data
  • Protein Serine-Threonine Kinases / metabolism*
  • Proteins / pharmacology
  • Saccharomyces cerevisiae / genetics
  • Signal Transduction*
  • Transfection
  • Transforming Growth Factor beta / pharmacology*


  • Bone Morphogenetic Proteins
  • Proteins
  • Transforming Growth Factor beta
  • Epidermal Growth Factor
  • Protein Serine-Threonine Kinases
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7

Associated data

  • GENBANK/D76446