Ligation of the T Cell Receptor Complex Results in Phosphorylation of Smad2 in T Lymphocytes

Abstract

TGF-β modulates immune responses by regulating T cell function. The Smad family of proteins has been recently shown to transduce signals for the TGF-β superfamily and Smad2 mediates TGF-β signaling. Here, we showed that TGF-β phosphorylated Smad2 and induced interaction between Smad2 and Smad4 in primary T cells and the Jurkat T cell line. Interestingly, ligation of the T cell receptor (TCR)/CD3 complex with anti-CD3 mAb also phosphorylated Smad2, but failed to induce interaction between Smad2 and Smad4 in the Jurkat T cell line. Phosphorylation of Smad2 via the TCR/CD3 complex was not abrogated by treatment with neutralizing antibody against TGF-β. Furthermore, PD98059, a MEK inhibitor, suppressed Smad2 phosphorylation by stimulation with anti-CD3 mAb in Jurkat T cell line. These findings indicated that not only TGF-β but also stimulation via the TCR/CD3 complex phosphorylated Smad2 through mitogen-activated protein (MAP) kinase cascades, suggesting that Smad2 may function in both TGF-β- and TCR/CD3 complex-mediated signaling pathways in T cells.