Lebrun J J, Takabe K, Chen Y, Vale W
Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Mol Endocrinol. 1999 Jan;13(1):15-23. doi: 10.1210/mend.13.1.0218.
Activins and other members of the transforming growth factor-beta-like superfamily of growth factors transduce their signals by interacting with two types of receptor serine/threonine kinases. The Smad proteins, a new family of intracellular mediators are involved in the signaling pathways of these receptors, but the initial stages of their activation as well as their specific functions remain to be defined. We report here that the pathway-specific Smad2 and 3 can form a complex with the activin receptor in a ligand-dependent manner. This complex formation is rapid but also transient. Indeed, soon after their association with the activin receptor, Smad2 and Smad3 are released into the cytoplasm where they interact with the common partner Smad4. These Smad complexes then mediate activin-induced transcription. Finally, we show that the inhibitory Smad7 can prevent the association of the two pathway-specific Smads with the activin receptor complex, thereby blocking the activin signal.
激活素以及转化生长因子-β样生长因子超家族的其他成员，通过与两种受体丝氨酸/苏氨酸激酶相互作用来传导信号。Smad蛋白是一类新的细胞内介质家族，参与这些受体的信号通路，但它们激活的初始阶段及其特定功能仍有待确定。我们在此报告，通路特异性的Smad2和Smad3能够以配体依赖的方式与激活素受体形成复合物。这种复合物的形成迅速但短暂。实际上，在它们与激活素受体结合后不久，Smad2和Smad3就被释放到细胞质中，在那里它们与共同伙伴Smad4相互作用。这些Smad复合物随后介导激活素诱导的转录。最后，我们表明抑制性Smad7可以阻止两种通路特异性Smad与激活素受体复合物的结合，从而阻断激活素信号。
