Department of Cell and Tissue Biology, and Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California at San Francisco, San Francisco CA 94143, USA.
Department of Cell and Tissue Biology, and Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California at San Francisco, San Francisco CA 94143, USA.
Trends Cell Biol. 2017 Sep;27(9):658-672. doi: 10.1016/j.tcb.2017.04.005. Epub 2017 May 25.
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 家族蛋白控制细胞生理、增殖和生长，并指导细胞分化，因此在正常发育和疾病中发挥关键作用。TGF-β 家族配体与细胞表面受体的异源二聚体复合物相互作用，然后激活 Smad 信号转导，从而指导基因表达的变化的机制通常被认为已经确立。尽管 TGF-β 诱导的 Smad 信号转导可能被视为具有可预测结果的线性信号通路，但该通路为细胞提供了一种灵活的手段来诱导不同的细胞反应。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与上下文相关的多种细胞反应，仍然存在一些基本问题。在取得进展的领域中，我们总结了有关细胞如何通过控制 TGF-β 受体来控制 TGF-β 反应性的新见解，以及 Smads 在指导细胞分化和细胞命运选择方面的关键作用和多功能性。
