A WD-domain protein that is associated with and phosphorylated by the type II TGF-beta receptor

Nature. 1995 Oct 12;377(6549):548-52. doi: 10.1038/377548a0.

Abstract

Transforming growth factor-beta (TGF-beta) is the prototype for a family of extracellular polypeptides that affect cell proliferation and differentiation, and tissue morphogenesis. 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. 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-containing 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • Eukaryotic Initiation Factor-3
  • Humans
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Phosphorylation
  • Plasmids
  • Protein Binding
  • Protein Serine-Threonine Kinases / metabolism*
  • Proteins / chemistry
  • Proteins / metabolism*
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Recombinant Proteins / metabolism
  • Transforming Growth Factor beta*

Substances

  • Eukaryotic Initiation Factor-3
  • Proteins
  • Receptors, Transforming Growth Factor beta
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • EIF3I protein, human
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II

Associated data

  • GENBANK/U36764
  • GENBANK/U36765