title: Non-Smad TGF-beta signals.
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 beta (TGF-beta) superfamily members to the nucleus. However, growing biochemical and developmental evidence supports the notion that alternative, non-Smad pathways also participate in TGF-beta signalling. Non-Smad signalling proteins have three general mechanisms by which they contribute to physiological responses to TGF-beta: (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-beta 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-beta 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.
authors.affiliation: Ludwig Institute for Cancer Research, Biomedical Center, Uppsala University, Box 595, SE 751 24 Uppsala, Sweden. aris.moustakas@licr.uu.se
authors.forename: Aristidis
authors.initials: A
authors.lastname: Moustakas
authors.forename: Carl-Henrik
authors.initials: CH
authors.lastname: Heldin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D025461:Feedback, Physiological / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D010766:Phosphorylation; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta