Transforming growth factor (TGF)-β family proteins control cell physiology, proliferation, and growth, and direct cell differentiation, thus playing key roles in normal development and disease. The mechanisms of how TGF-β family ligands interact with heteromeric complexes of cell surface receptors to then activate Smad signaling that directs changes in gene expression are often seen as established. Even though TGF-β-induced Smad signaling may be seen as a linear signaling pathway with predictable outcomes, this pathway provides cells with a versatile means to induce different cellular responses. Fundamental questions remain as to how, at the molecular level, TGF-β and TGF-β family proteins activate the receptor complexes and induce a context-dependent diversity of cell responses. Among the areas of progress, we summarize new insights into how cells control TGF-β responsiveness by controlling the TGF-β receptors, and into the key roles and versatility of Smads in directing cell differentiation and cell fate selection.

转化生长因子（TGF）-β家族蛋白控制细胞的生理，增殖和生长以及直接的细胞分化，因此在正常发育和疾病中起着关键作用。人们通常认为，TGF-β家族配体如何与细胞表面受体的异聚复合物相互作用，然后激活指导基因表达变化的Smad信号传导机制。即使TGF-β诱导的Smad信号传导可被视为具有可预测结果的线性信号传导途径，但该途径为细胞提供了诱导不同细胞反应的通用手段。关于在分子水平上TGF-β和TGF-β家族蛋白如何激活受体复合物并诱导细胞反应的背景依赖性多样性，仍然存在根本问题。在进步领域中，