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.
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