PHOSPHORYLATION-DEPENDENT INTERACTION OF THE CYTOPLASMIC DOMAINS OF THE TYPE-I AND TYPE-II TRANSFORMING GROWTH-FACTOR-BETA RECEPTORS

Transforming growth factor-beta (TGF-beta) transduces signals through its type I and type II receptors. Both receptor types have previously been shown to interact in a heteromeric complex in the presence of TGF -beta. We have now characterized these interactions between both recep tor types using a combination of yeast two-hybrid interaction assays a nd coimmunoprecipitation analyses. Our results indicate a direct assoc iation between the cytoplasmic domains of the two receptor types. Muta tion analysis of these cytoplasmic domains reveals that this direct in teraction requires kinase activity and, thus, depends on phosphorylati on, probably via a transphosphorylation mechanism. Furthermore, the tw o receptor types already have an inherent affinity for each other in t he absence of TGF-beta, and the heteromeric complex can be detected in coimmunoprecipitation under these conditions. Taken together, our res ults reveal a novel mechanism of receptor complex formation, whereby t wo different cytoplasmic domains directly associate with each other. T his interaction may play a major role in activation of serine/threonin e kinase receptors.