Derynck Rik, Zhang Ying E
Department of Growth and Development, University of California at San Francisco, San Francisco, California 94143-0640, USA.
Nature. 2003 Oct 9;425(6958):577-84. doi: 10.1038/nature02006.
Transforming growth factor-beta (TGF-beta) proteins regulate cell function, and have key roles in development and carcinogenesis. The intracellular effectors of TGF-beta signalling, the Smad proteins, are activated by receptors and translocate into the nucleus, where they regulate transcription. Although this pathway is inherently simple, combinatorial interactions in the heteromeric receptor and Smad complexes, receptor-interacting and Smad-interacting proteins, and cooperation with sequence-specific transcription factors allow substantial versatility and diversification of TGF-beta family responses. Other signalling pathways further regulate Smad activation and function. In addition, TGF-beta receptors activate Smad-independent pathways that not only regulate Smad signalling, but also allow Smad-independent TGF-beta responses.
转化生长因子-β（TGF-β）蛋白调节细胞功能，在发育和致癌过程中起关键作用。TGF-β信号传导的细胞内效应器Smad蛋白被受体激活并转运到细胞核中，在那里它们调节转录。尽管这条途径本质上很简单，但异源三聚体受体和Smad复合物中的组合相互作用、与受体相互作用和Smad相互作用的蛋白，以及与序列特异性转录因子的合作，使得TGF-β家族反应具有显著的多样性和特异性。其他信号通路进一步调节Smad的激活和功能。此外，TGF-β受体激活不依赖Smad的途径，这些途径不仅调节Smad信号传导，还允许产生不依赖Smad的TGF-β反应。
