Identification of a member of the MAPKKK family as a potential mediator of TGF-beta 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-o (TGF-β). Furthermore, kinase activity of TAK1 was stimulated in response to TGF-P and bone morphogenetic protein. These results suggest that TAK1 functions as a mediator in the signaling pathway of TGF-β superfamily members.
Activation of MAPKs after ligand binding to various receptors has been correlated with numerous cellular responses, including proliferation, differentiation, and regulation of specific metabolic pathways in differentiated cell types. The [...]