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 bet a eukaryotic signaling module that converts receptor signals into vari ous 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 mous e protein kinase (TAK1) distinct from other members of the MAPKKK fami ly. TAK1 was shown to participate in regulation of transcription by tr ansforming 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 t he signaling pathway of TGF-beta superfamily members.