| Title | Modulation of the transforming growth factor-beta1-induced Smad phosphorylation by the extracellular matrix receptor beta1-integrin. | | Author(s) | Hamajima H, Ozaki I, Zhang H, Iwane S, Kawaguchi Y, Eguchi Y, Matsuhashi S, Mizuta T, Matsuzaki K, Fujimoto K | | Institution | Department of Internal Medicine, Saga Medical School, Saga University, Saga 849-8501, Japan. | | Source | Int J Oncol 2009 Dec; 35(6):1441-1447. | | Abstract | 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19885568 |
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