Datta P K, Chytil A, Gorska A E, Moses H L
Department of Cell Biology and Vanderbilt Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6838, USA.
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.
转化生长因子-β1（TGF-β1）是一大类调节多种生物学过程的蛋白质家族的原型。对TGF-β的多效性反应是通过配体诱导的I型（TβR-I）和II型（TβR-II）丝氨酸 - 苏氨酸激酶受体形成异源复合物介导的。多项研究表明，TβR-II作为主要受体，结合TGF-β并磷酸化TβR-I，其激酶活性随后传递信号。因此，与I型受体相互作用的细胞内蛋白质可能在TGF-β信号传导中发挥重要作用。我们鉴定了一种新型的含WD结构域的蛋白质，命名为STRAP（丝氨酸 - 苏氨酸激酶受体相关蛋白），它在酵母双杂交系统中与TβR-I相互作用。STRAP在体内与功能性TβR-I和TβR-II都相关联。STRAP的过表达导致TGF-β介导的转录激活受到抑制。通过TGF-β依赖性转录报告基因检测，它还与Smad7协同抑制TGF-β信号传导，但与Smad6没有协同作用。从酵母到哺乳动物都存在STRAP基因，这表明其在真核生物中具有进化上保守的功能。这些数据表明STRAP在TGF-β信号转导中具有潜在作用。
