Transforming growth factor beta signaling mediators and modulators

Transforming growth factor beta is a multi-functional growth and differenti ation factor responsible for regulating many diverse biological processes i n both vertebrate and invertebrate species, Among the most dramatic of TGF beta's effects are those associated with specification of cell fates during development and inhibition of cell cycle progression. The core TGF beta si gnaling pathway has now been described using a synergistic combination of g enetic and biochemical approaches. Transmembrane receptors with intrinsic p rotein serine kinase activity bind ligand in the extracellular milieu and t hen phosphorylate intracellular proteins known as Smads. Phosphorylated Sma ds form heterooligomers and translocate into the nucleus where they can mod ulate transcriptional responses. More recent studies indicate that many oth er proteins serve as modulators of Smad activity, and ultimately define spe cific cellular responses to TGF beta. Here we describe both the simplistic core TGF beta signaling pathway and the growing number of proteins that imp inge on this pathway at the level of Smad function to either enhance or inh ibit TGF beta responses (C) 2000 Elsevier Science B.V. All rights reserved.