Cell biology of Smad2/3 linker region phosphorylation in vascular smooth muscle

Rezaei, Hossein B., Kamato, Danielle, Ansari, Ghazaleh, Osman, Narin and Little, Peter J. (2012) Cell biology of Smad2/3 linker region phosphorylation in vascular smooth muscle. Clinical and Experimental Pharmacology and Physiology, 39 8: 661-667. doi:10.1111/j.1440-1681.2011.05592.x

Author Rezaei, Hossein B.
Kamato, Danielle
Ansari, Ghazaleh
Osman, Narin
Little, Peter J.
Title Cell biology of Smad2/3 linker region phosphorylation in vascular smooth muscle
Journal name Clinical and Experimental Pharmacology and Physiology   Check publisher's open access policy
ISSN 0305-1870
Publication date 2012-08
Year available 2012
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1111/j.1440-1681.2011.05592.x
Open Access Status Not Open Access
Volume 39
Issue 8
Start page 661
End page 667
Total pages 7
Place of publication Richmond, VIC Australia
Publisher Wiley-Blackwell Publishing Asia
Language eng
Formatted abstract
1. The transforming growth factor (TGF)-β superfamily of ligands regulates a diverse set of cellular functions. Transforming growth factor-β induces its biological effects through Type I and Type II transmembrane receptors that have serine/threonine kinase activities and weak tyrosine kinase activity. In vascular smooth muscle, TGF-β binds to the TGF-β Type II receptor (TβRII) at the cell surface, recruiting the Type I receptor (TβRI) to form a heterocomplex. Consequently, after phosphorylation and activation of TβRI, the transcription factors receptor activated (R-) Smad2 and Smad3 are recruited and activated through phosphorylation of C terminal residues. Overall, Smad2/3 and co-Smad4 have similar structures consisting of three regions an N-terminal MH1 domain, a C-terminal MH2 domain and a central linker region.

2. Phosphorylation of the Smad linker region appears to have an important role in the regulation of Smad activity and function. The mitogen-activated protein kinase (MAPK) family, CDK2, CDK4 and calcium–calmodulin dependent kinase are the main kinases that phosphorylate sites in the linker region. The role of the linker region includes enabling the formation of Smad homo-oligomers and provision of phosphorylation sites for MAPK and other kinases. In some instances, linker region phosphorylation regulates the inhibition of the nuclear translocation of Smads.

3. In the present review, we describe TGF-β signalling through Smad2/3 and the importance of the linker region in the regulation and expression of genes induced by TGF-β superfamily ligands in the context of vascular smooth muscle.
Keyword Phosphorylation
Transforming growth factor-β
Vascular smooth muscle
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collection: School of Pharmacy Publications
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