Open AccessModulation of the transforming growth factor-β1-induced Smad phosphorylation by the extracellular matrix receptor β1-integrin
Author(s) -
; Ozaki
Publication year - 2009
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo_00000463
Subject(s) - smad , phosphorylation , r smad , integrin , microbiology and biotechnology , biology , transforming growth factor , integrin, beta 6 , extracellular matrix , transfection , smad2 protein , integrin alpha m , signal transduction , receptor , growth factor , tgf alpha , cell culture , biochemistry , genetics
Integrins, heterodimeric receptors for the extracellular matrix, are known to modulate transforming growth factor-beta1 (TGF-beta1)-mediated cell behavior. However, the interplay between beta1-integrin and Smad signaling, regulated by TGF-beta1, is not clearly understood. This study focuses on the alterations of the regulatory Smads (R-Smads) by TGF-beta1 in beta1-integrin-transfected HepG2 cells. The phosphorylation at the C-terminal site of R-Smads by TGF-beta1 was impaired in the beta1-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-beta1-induced Smad transcriptional activity. These results suggest that beta1-integrin impairs the TGF-beta1-mediated signals through the altered phosphorylation of the R-Smads.