Smad linker region phosphorylation is a signalling pathway in its own right and not only a modulator of canonical TGF-β signalling
- Resource Type
- Authors
- Suowen Xu; Benjamin P. Ross; Raafat Mohamed; Bich Hang Do; Narin Osman; Peter J. Little; Danielle Kamato
- Source
- Cellular and molecular life sciences : CMLS. 77(2)
- Subject
- Pharmacology
0303 health sciences
Chemistry
Kinase
030302 biochemistry & molecular biology
Gene Expression
Smad Proteins
Cell Biology
SMAD
Hedgehog signaling pathway
Cell biology
Serine
03 medical and health sciences
Cellular and Molecular Neuroscience
Transforming Growth Factor beta
Molecular Medicine
Phosphorylation
Animals
Humans
Molecular Biology
Transcription factor
Linker
Transforming growth factor
Signal Transduction
- Language
- ISSN
- 1420-9071
Transforming growth factor (TGF)-β signalling pathways are intensively investigated because of their diverse association with physiological and pathophysiological states. Smad transcription factors are the key mediators of TGF-β signalling. Smads can be directly phosphorylated in the carboxy terminal by the TGF-β receptor or in the linker region via multiple intermediate serine/threonine kinases. Growth factors in addition to hormones and TGF-β can activate many of the same kinases which can phosphorylate the Smad linker region. Historically, Smad linker region phosphorylation was shown to prevent nuclear translocation of Smads and inhibit TGF-β signalling pathways; however, it was subsequently shown that Smad linker region phosphorylation can be a driver of gene expression. This review will cover the signalling pathways of Smad linker region phosphorylation that drive the expression of genes involved in pathology and pathophysiology. The role of Smad signalling in cell biology is expanding rapidly beyond its role in TGF-β signalling and many signalling paradigms need to be re-evaluated in terms of Smad involvement.