CLONING AND CHARACTERIZATION OF A TRANSMEMBRANE SERINE KINASE THAT ACTS AS AN ACTIVIN TYPE-I RECEPTOR

Activin type II receptors are transmembrane protein-serine/threonine k inases. By using a reverse-transcription PCR assay to screen for prote in kinase sequences, we isolated a cDNA done, activin X1 receptor, fro m rat brain that encodes a 55-kDa transmembrane protein-serine kinase which is structurally related to other receptors in this kinase subfam ily. The predicted protein consists of 509 amino acids, and the kinase domain shows 40% and 37% identity to the activin and transforming gro wth factor beta type II receptors, respectively. No activin-binding wa s observed when activin X1 receptor was expressed alone in COS-M6 cell s; however, coexpression with type II activin receptors gave rise to a 68-kDa affinity-labeled complex in addition to the 85-kDa type II rec eptor complex. The size of this cross-linked band is consistent with t he size of the type I activin receptor; furthermore, activin X1 recept or associated with type II receptors, as judged by coimmunoprecipitati on with type II receptor antibodies. These data suggest that activin X 1 receptor can serve as an activin type I receptor and that the divers e biological effects of activins may be mediated by a complex formed b y the interaction of two transmembrane protein-serine kinases.