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

Datta PK, Chytil A, Gorska AE, Moses HL
J Biol Chem. 1998 273 (52): 34671-4

PMID: 9856985 · 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.

MeSH Terms (15)

Adaptor Proteins, Signal Transducing Amino Acid Sequence Animals Aspartic Acid Cloning, Molecular Mice Molecular Sequence Data Protein Binding Proteins Receptors, Growth Factor Receptors, Transforming Growth Factor beta Signal Transduction Transcriptional Activation Transforming Growth Factor beta Tryptophan

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