Dose-dependent cross-talk between the transforming growth factor-beta and interleukin-1 signaling pathways.

ABSTRACT: Some tumor cell lines secrete high concentrations of TGFbeta or IL-1. Similarly high concentrations of each of these cytokines cross-activate the other pathway: TGFbeta activates NFkappaB, and IL-1beta activates Smads. The IL-1 signaling components IRAK, MyD88, TRAF6, and TAK1 are all required for cross-activation of NFkappaB by TGFbeta. Knockdown experiments revealed that both TGFbeta receptor subunits are required for IL-1beta to activate Smads, and the IL-1 receptor is required for TGFbeta to activate NFkappaB. Coimmunoprecipitations showed that either TGFbeta or IL-1beta stimulate ligand-dependent association of all three receptor subunits. Furthermore, cross-talk between the TGFbeta and IL-1 signaling pathways leads to dose-dependent cross-control of gene expression. These interaction

SUBMITTER: Lu T 

PROVIDER: S-EPMC1810327 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature