A WD-DOMAIN PROTEIN THAT IS ASSOCIATED WITH AND PHOSPHORYLATED BY THE TYPE-II TGF-BETA RECEPTOR

TRANSFORMING growth factor-beta (TGF-beta) is tbe prototype for a family of extracellular polypeptides that affect cell proliferation and differentiation, and tissue morphogenesis(1). TGF-beta signalling is mediated by two types of serine/threonine kinase receptors, the type I and II receptors, which are able to form a heteromeric complex(2). No cytoplasmic proteins that associate with these receptors in vivo, or are their kinase targets, have yet been described. We have now identified a WD-domain-containiag protein, TRIP-1, which specifically associates with the type II TGF-beta receptor in a kinase-dependent way. TRIP-1 does not interact with the type II activin or type I receptors, but associates with the heteromeric TGF-beta receptor complex, TRIP-1 is phosphorylated on serine and threonine by the receptor kinase, strongly suggesting that it has a role in TGF-beta signalling. This is supported by coexpression of TRIP-1 and type II receptor during development. The existence of TRIP-1 homologues in plant and yeast suggests a conserved function in all eukaryotes.