Specificity and versatility in tgf-beta signaling through Smads.
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.
Feng
Xin-Hua
XH
Department of Molecular and Cellular Biology, Biology of Inflammation Center, Baylor College of Medicine, Houston, Texas 77030, USA. xfeng@bcm.tmc.edu
Derynck
Rik
R
D000818:Animals; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism; D005544:Forecasting; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D012680:Sensitivity and Specificity; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000502:physiology*
D008024:Ligands; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D052004:Bone Morphogenetic Protein Receptors