Affiliation:
1. Ludwig Institute for Cancer Research, Biomedical Center, Uppsala University, Box 595, SE 751 24 Uppsala, Sweden
Abstract
During the past 10 years, it has been firmly established that Smad pathways are central mediators of signals from the receptors for transforming growth factor β (TGF-β) superfamily members to the nucleus. However, growing biochemical and developmental evidence supports the notion that alternative, non-Smad pathways also participate in TGF-β signalling. Non-Smad signalling proteins have three general mechanisms by which they contribute to physiological responses to TGF-β: (1) non-Smad signalling pathways directly modify (e.g. phosphorylate) the Smads and thus modulate the activity of the central effectors; (2) Smads directly interact and modulate the activity of other signalling proteins (e.g. kinases), thus transmitting signals to other pathways; and (3) the TGF-β receptors directly interact with or phosphorylate non-Smad proteins, thus initiating parallel signalling that cooperates with the Smad pathway in eliciting physiological responses. Thus, non-Smad signal transducers under the control of TGF-β provide quantitative regulation of the signalling pathway, and serve as nodes for crosstalk with other major signalling pathways, such as tyrosine kinase, G-protein-coupled or cytokine receptors.
Publisher
The Company of Biologists
Cited by
960 articles.
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