Identification of STRAP, a novel WD domain protein in transforming growth factor-beta signaling.
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.
Datta
P K
PK
Department of Cell Biology and Vanderbilt Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6838, USA.
Chytil
A
A
Gorska
A E
AE
Moses
H L
HL
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid; D003001:Cloning, Molecular; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D011506:Proteins; D016601:RNA-Binding Proteins; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014364:Tryptophan
D048868:Adaptor Proteins, Signal Transducing; D011506:Proteins; D016601:RNA-Binding Proteins; D017978:Receptors, Growth Factor; D018125:Receptors, Transforming Growth Factor beta; C116758:STRAP protein, mouse; D016212:Transforming Growth Factor beta; D001224:Aspartic Acid; D014364:Tryptophan