Modulation of the transforming growth factor-β1-induced Smad phosphorylation by the extracellular matrix receptor β1-integrin
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- Published online on: December 1, 2009 https://doi.org/10.3892/ijo_00000463
- Pages: 1441-1447
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Abstract
Integrins, heterodimeric receptors for the extracellular matrix, are known to modulate transforming growth factor-β1 (TGF-β1)-mediated cell behavior. However, the interplay between β1-integrin and Smad signaling, regulated by TGF-β1, is not clearly understood. This study focuses on the alterations of the regulatory Smads (R-Smads) by TGF-β1 in β1-integrin-transfected HepG2 cells. The phosphorylation at the C-terminal site of R-Smads by TGF-β1 was impaired in the β1-integrin-transfected cells. However, the R-Smads were constitutively phosphorylated at the linker region in a MAP kinase-dependent manner. Furthermore, the expression of a mutant Smad3, that lacks the phosphorylation sites in the linker region, restored the TGF-β1-induced Smad transcriptional activity. These results suggest that β1-integrin impairs the TGF-β1-mediated signals through the altered phosphorylation of the R-Smads.
