Ligation of the T cell receptor complex results in phosphorylation of Smad2 in T lymphocytes.
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.
Mamura
M
M
Department of Internal Medicine II, Chiba University School of Medicine, Chiba, Japan.
Nakao
A
A
Goto
D
D
Kato
M
M
Saito
Y
Y
Iwamoto
I
I
D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D017252:CD3 Complex / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D019169:Jurkat Cells; D048369:MAP Kinase Kinase 1; D051379:Mice; D008807:Mice, Inbred BALB C; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D051899:Smad2 Protein; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D017931:DNA Primers; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; C497782:SMAD2 protein, human; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; C497784:Smad2 protein, rat; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; C482127:Map2k1 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one