Identification of STRAP, a novel WD domain protein in transforming growth factor-beta signaling

J Biol Chem. 1998 Dec 25;273(52):34671-4. doi: 10.1074/jbc.273.52.34671.


Transforming growth factor-beta1 (TGF-beta1) is the prototype of a large family of proteins that regulate a variety of biological processes. The pleiotropic responses to TGF-beta are mediated via ligand-induced heteromeric complex formation by type I (TbetaR-I) and type II (TbetaR-II) serine-threonine kinase receptors. Several studies have shown that TbetaR-II acts as a primary receptor, binding TGF-beta and phosphorylating TbetaR-I, whose kinase activity then propagates the signals. Therefore, intracellular proteins that interact with type I receptors are likely to play important roles in TGF-beta signaling. We have identified a novel WD domain-containing protein, designated STRAP (serine-threonine kinase receptor-associated protein), which interacts with TbetaR-I in a yeast two-hybrid system. STRAP associates with both functional TbetaR-I and TbetaR-II in vivo. Overexpression of STRAP leads to inhibition of TGF-beta-mediated transcriptional activation. It also shows synergistic inhibition of TGF-beta signaling in concert with Smad7, but not with Smad6, as measured by TGF-beta-dependent transcriptional reporters. The existence of the STRAP gene from yeast to mammals indicates an evolutionarily conserved function in eukaryotes. The data suggest a potential role for STRAP in TGF-beta signal transduction.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Aspartic Acid
  • Cloning, Molecular
  • Mice
  • Molecular Sequence Data
  • Protein Binding
  • Proteins*
  • RNA-Binding Proteins
  • Receptors, Growth Factor / genetics
  • Receptors, Growth Factor / metabolism
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Signal Transduction
  • Transcriptional Activation
  • Transforming Growth Factor beta / metabolism*
  • Tryptophan


  • Adaptor Proteins, Signal Transducing
  • Proteins
  • RNA-Binding Proteins
  • Receptors, Growth Factor
  • Receptors, Transforming Growth Factor beta
  • STRAP protein, mouse
  • Transforming Growth Factor beta
  • Aspartic Acid
  • Tryptophan

Associated data

  • GENBANK/AF096285