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First published online August 16, 2005
doi: 10.1242/10.1242/jcs.02554
Commentary |
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala University, Box 595, SE 751 24 Uppsala, Sweden
* Author for correspondence (e-mail: aris.moustakas{at}licr.uu.se)
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 ß (TGF-ß) superfamily members to the nucleus. However, growing biochemical and developmental evidence supports the notion that alternative, non-Smad pathways also participate in TGF-ß signalling. Non-Smad signalling proteins have three general mechanisms by which they contribute to physiological responses to TGF-ß: (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-ß 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-ß 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.
Key words: BMP, MAPK, PI3K, Phosphatase, Ras, Rho, Smad, TGF-ß
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