Back to Search
Start Over
Phosphorylation of threonine 276 in Smad4 is involved in transforming growth factor-[beta]-induced nuclear accumulation
- Source :
- The American Journal of Physiology. Oct, 2003, Vol. 285 Issue 4, pC823, 8 p.
- Publication Year :
- 2003
-
Abstract
- Smad4, the common Smad, is central for transforming growth factor (TGF)-[beta] superfamily ligand signaling. Smad4 has been shown to be constitutively phosphorylated (Nakao A, Imamura T, Souchelnytskyi S, Kawabata M, Ishisaki A, Oeda E, Tamaki K, Hanai J, Heldin C-H, Miyazono K, and ten Dijke P. EMBO J 16: 5353-5362, 1997), but the site(s) of phosphorylation, the kinase(s) that performs this phosphorylation, and the significance of the phosphorylation of Smad4 are currently unknown. This report describes the identification of a consensus ERK phosphorylation site in the linker region of Smad4 at [Thr.sup.276]. Our data show that ERK can phosphorylate Smad4 in vitro but not Smad4 with mutated [Thr.sup.276]. Flag-tagged Smad4-T276A mutant protein accumulates less efficiently in the nucleus after stimulation by TGF-[beta] and is less efficient in generating a transcriptional response than Smad4 wild-type protein. Tryptic phosphopeptide mapping identified a phosphopeptide in Smad4 wild-type protein that was absent in phosphorylated Smad4T276A mutant protein. Our results suggest that MAP kinase can phosphorylate [Thr.sup.276] of Smad4 and that phosphorylation can lead to enhanced TGF-[beta]-induced nuclear accumulation and, as a consequence, enhanced transcriptional activity of Smad4. signal transduction; mitogenoactivated protein kinase; phosphopeptide mapping; extracellular signal-regulated kinase phosphorylation site; luciferase reporter
- Subjects :
- Transforming growth factors -- Physiological aspects
Biological sciences
Subjects
Details
- Language :
- English
- ISSN :
- 00029513
- Volume :
- 285
- Issue :
- 4
- Database :
- Gale General OneFile
- Journal :
- The American Journal of Physiology
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.110113257