Specificity and versatility in tgf-beta signaling through Smads.

Department of Molecular and Cellular Biology, Biology of Inflammation Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Annual Review of Cell and Developmental Biology (Impact Factor: 20.24). 02/2005; 21:659-93. DOI: 10.1146/annurev.cellbio.21.022404.142018
Source: PubMed

ABSTRACT The TGF-beta family comprises many structurally related differentiation factors that act through a heteromeric receptor complex at the cell surface and an intracellular signal transducing Smad complex. The receptor complex consists of two type II and two type I transmembrane serine/threonine kinases. Upon phosphorylation by the receptors, Smad complexes translocate into the nucleus, where they cooperate with sequence-specific transcription factors to regulate gene expression. The vertebrate genome encodes many ligands, fewer type II and type I receptors, and only a few Smads. In contrast to the perceived simplicity of the signal transduction mechanism with few Smads, the cellular responses to TGF-beta ligands are complex and context dependent. This raises the question of how the specificity of the ligand-induced signaling is achieved. We review the molecular basis for the specificity and versatility of signaling by the many ligands through this conceptually simple signal transduction mechanism.

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