title: Modulation of the transforming growth factor-beta1-induced Smad phosphorylation by the extracellular matrix receptor beta1-integrin.
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.
authors.affiliation: Department of Internal Medicine, Saga Medical School, Saga University, Saga 849-8501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamajima
authors.forename: Iwata
authors.initials: I
authors.lastname: Ozaki
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Shinji
authors.initials: S
authors.lastname: Iwane
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Eguchi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Matsuhashi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Mizuta
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuzaki
authors.forename: Kazuma
authors.initials: K
authors.lastname: Fujimoto
mesh_terms: D015153:Blotting, Western; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins / Q000378:metabolism*; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D019012:Integrin beta1; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1