Mamura M, Nakao A, Goto D, Kato M, Saito Y, Iwamoto I
Department of Internal Medicine II, Chiba University School of Medicine, Chiba, Japan.
Biochem Biophys Res Commun. 2000 Feb 5;268(1):124-7. doi: 10.1006/bbrc.2000.2086.
TGF-beta modulates immune responses by regulating T cell function. The Smad family of proteins has been recently shown to transduce signals for the TGF-beta superfamily and Smad2 mediates TGF-beta signaling. Here, we showed that TGF-beta 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-beta. 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-beta 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-beta- and TCR/CD3 complex-mediated signaling pathways in T cells.
转化生长因子β（TGF-β）通过调节T细胞功能来调控免疫反应。近来研究表明，Smad蛋白家族可转导TGF-β超家族的信号，其中Smad2介导TGF-β信号传导。在此，我们发现TGF-β可使原代T细胞和Jurkat T细胞系中的Smad2磷酸化，并诱导Smad2与Smad4相互作用。有趣的是，用抗CD3单克隆抗体连接T细胞受体（TCR）/CD3复合物也能使Smad2磷酸化，但在Jurkat T细胞系中却不能诱导Smad2与Smad4相互作用。通过TCR/CD3复合物使Smad2磷酸化，不会因用抗TGF-β中和抗体处理而被消除。此外，MEK抑制剂PD98059可抑制Jurkat T细胞系中抗CD3单克隆抗体刺激引起的Smad2磷酸化。这些发现表明，不仅TGF-β，而且通过TCR/CD3复合物的刺激均可通过丝裂原活化蛋白（MAP）激酶级联反应使Smad2磷酸化，这提示Smad2可能在T细胞中TGF-β和TCR/CD3复合物介导的信号通路中均发挥作用。
