Dynamic allostery: a novel mechanism regulating autocrine and paracrine TGF-β signalling

Abstract

In a recent landmark study published in Cell¹ Jin and colleagues convincingly demonstrated that mature transforming growth factor-β1 (mTGF-β1) can be activated without release from its latent form (L-TGF-β), and that binding of unreleased mTGF-β to its receptors induces autocrine signalling rather than the conventional paracrine effects. These findings contradict the current dogma that mTGF-β1 requires physical dissociation and release from L-TGF-β1 in order to be able to bind to the TGF-β receptors (TGF-βRs) and signal.