IDENTIFICATION OF HUMAN ACTIVIN AND TGF-BETA TYPE-I RECEPTORS THAT FORM HETEROMERIC KINASE COMPLEXES WITH TYPE-II RECEPTORS

Transforming growth factor beta (TGFbeta) and activin each bind to pairs of membrane proteins, known as receptor types I and II, that associate to form a signaling complex. We report that TSR-I and ActR-I, two human transmembrane serine/threonine kinases distantly related to TGFbeta and activin type II receptors, act as type I receptors for these factors. TSR-I is a type I receptor shared by TGFbeta and activin, whereas ActR-I is an activin type I receptor. ActR-I, but not TSR-I, signals a particular transcriptional response in concert with activin type II receptors. The results indicate that type I receptors are transmembrane protein kinases that associate with type II receptors to generate diverse heteromeric serine/threonine kinase complexes of different signaling capacities.