Abstract
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.
Copyright 2000 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal
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Base Sequence
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CD3 Complex / metabolism
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DNA Primers / genetics
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Enzyme Inhibitors / pharmacology
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Flavonoids / pharmacology
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Humans
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In Vitro Techniques
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Jurkat Cells
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MAP Kinase Kinase 1
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Mice
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Mice, Inbred BALB C
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Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
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Phosphorylation
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Protein Serine-Threonine Kinases*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Receptors, Antigen, T-Cell / chemistry
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Receptors, Antigen, T-Cell / metabolism*
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Signal Transduction
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Smad2 Protein
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism*
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Trans-Activators / chemistry
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transforming Growth Factor beta / antagonists & inhibitors
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Transforming Growth Factor beta / metabolism
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Transforming Growth Factor beta / pharmacology
Substances
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Antibodies, Monoclonal
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CD3 Complex
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DNA Primers
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DNA-Binding Proteins
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Enzyme Inhibitors
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Flavonoids
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RNA, Messenger
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Receptors, Antigen, T-Cell
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SMAD2 protein, human
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Smad2 Protein
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Smad2 protein, mouse
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Smad2 protein, rat
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Trans-Activators
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Transforming Growth Factor beta
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Protein Serine-Threonine Kinases
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MAP Kinase Kinase 1
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MAP2K1 protein, human
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Map2k1 protein, mouse
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Mitogen-Activated Protein Kinase Kinases
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one