Format

Send to

Choose Destination
Cell Res. 2009 Jan;19(1):8-20. doi: 10.1038/cr.2008.327.

Phospho-control of TGF-beta superfamily signaling.

Author information

1
Michael E. DeBakey Department of Surgery, Department of Molecular & Cellular Biology and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.

Abstract

Members of the transforming growth factor-beta (TGF-beta) family control a broad range of cellular responses in metazoan organisms via autocrine, paracrine, and endocrine modes. Thus, aberrant TGF-beta signaling can play a key role in the pathogenesis of several diseases, including cancer. TGF-beta signaling pathways are activated by a short phospho-cascade, from receptor phosphorylation to the subsequent phosphorylation and activation of downstream signal transducers called R-Smads. R-Smad phosphorylation state determines Smad complex assembly/disassembly, nuclear import/export, transcriptional activity and stability, and is thus the most critical event in TGF-beta signaling. Dephosphorylation of R-Smads by specific phosphatases prevents or terminates TGF-beta signaling, highlighting the need to consider Smad (de)phosphorylation as a tightly controlled and dynamic event. This article illustrates the essential roles of reversible phosphorylation in controlling the strength and duration of TGF-beta signaling and the ensuing physiological responses.

PMID:
19114991
PMCID:
PMC2929013
DOI:
10.1038/cr.2008.327
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center