Lateral signaling enhances TGF-beta response complexity.
TGF-beta elicits context-dependent and cell-specific effects that often appear conflicting, such as stimulation or inhibition of growth, apoptosis or differentiation. It is puzzling how such a diverse array of responses can result from binding of TGF-beta to a single receptor complex that activates a seemingly straightforward signal-transduction scheme dependent on shuttling of Smad transducer proteins from the receptor to the nucleus. Here, we discuss a novel paradigm for TGF-beta signaling in endothelial cells in which the same ligand can induce opposing effects mediated by activation of two different classes of Smads through a chimeric receptor complex.
Byfield
Stacey DaCosta
SD
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of health, Bethesda, MD 20892-5055, USA.
Roberts
Anita B
AB
D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins; D015534:Trans-Activators / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051785:Smad Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases