Akhurst Rosemary J, Padgett Richard W
Helen Diller Family Comprehensive Cancer Center and Department of Anatomy, University of California at San Francisco, San Francisco, CA 94158-9001, USA.
Waksman Institute, Department of Molecular Biology and Biochemistry, and Cancer Institute of New Jersey, Rutgers University, Piscataway, NJ 08854-8020, USA.
Sci Signal. 2015 Oct 20;8(399):re10. doi: 10.1126/scisignal.aad0416.
The highly conserved wiring of the SMAD-dependent transforming growth factor β (TGFβ) superfamily signaling pathway has been mapped over the last 20 years after molecular discovery of its component parts. Numerous alternative TGFβ-activated signaling pathways that elicit SMAD-independent biological responses also exist. However, the molecular mechanisms responsible for the renowned context dependency of TGFβ signaling output remains an active and often confounding area of research, providing a prototype relevant to regulation of other signaling pathways. Highlighting discoveries presented at the 9th FASEB meeting, The TGFβ Superfamily: Signaling in Development and Disease (July 12-17th 2015 in Snowmass, Colorado), this Review outlines research into the rich contextual nature of TGFβ signaling output and offers clues for therapeutic advances.
在过去20年里,随着SMAD依赖的转化生长因子β(TGFβ)超家族信号通路各组成部分在分子层面被发现,其高度保守的信号传导线路已被绘制出来。此外,还存在许多能引发不依赖SMAD的生物学反应的替代性TGFβ激活信号通路。然而,导致TGFβ信号输出具有著名的背景依赖性的分子机制,仍是一个活跃且常常令人困惑的研究领域,为其他信号通路的调控提供了一个相关的范例。本综述突出了在第九届FASEB会议“TGFβ超家族:发育与疾病中的信号传导”(2015年7月12日至17日于科罗拉多州斯诺马斯)上展示的发现,概述了对TGFβ信号输出丰富背景性质的研究,并为治疗进展提供了线索。