Transforming growth factor-beta (TGF-beta1) activates TAK1 via TAB1-mediated autophosphorylation, independent of TGF-beta receptor kinase activity in mesangial cells.

ABSTRACT: Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that signals through the interaction of type I (TbetaRI) and type II (TbetaRII) receptors to activate distinct intracellular pathways. TAK1 is a serine/threonine kinase that is rapidly activated by TGF-beta1. However, the molecular mechanism of TAK1 activation is incompletely understood. Here, we propose a mechanism whereby TAK1 is activated by TGF-beta1 in primary mouse mesangial cells. Under unstimulated conditions, endogenous TAK1 is stably associated with TbetaRI. TGF-beta1 stimulation causes rapid dissociation from the receptor and induces TAK1 phosphorylation. Deletion mutant analysis indicates that the juxtamembrane region including the GS domain of TbetaRI is crucial for its interaction with TAK1. Both Tbeta

SUBMITTER: Kim SI 

PROVIDER: S-EPMC2755952 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature