Abstract
T lymphocytes express several low molecular weight transmembrane adaptor proteins that recruit src homology (SH)2 domain-containing intracellular molecules to the cell membrane via tyrosine-based signaling motifs. We describe here a novel molecule of this group termed SIT (SHP2 interacting transmembrane adaptor protein). SIT is a disulfide-linked homodimeric glycoprotein that is expressed in lymphocytes. After tyrosine phosphorylation by src and possibly syk protein tyrosine kinases SIT recruits the SH2 domain-containing tyrosine phosphatase SHP2 via an immunoreceptor tyrosine-based inhibition motif. Overexpression of SIT in Jurkat cells downmodulates T cell receptor- and phytohemagglutinin-mediated activation of the nuclear factor of activated T cells (NF-AT) by interfering with signaling processes that are probably located upstream of activation of phospholipase C. However, binding of SHP2 to SIT is not required for inhibition of NF-AT induction, suggesting that SIT not only regulates NF-AT activity but also controls NF-AT unrelated pathways of T cell activation involving SHP2.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Amino Acid Sequence
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Carrier Proteins / chemistry
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Carrier Proteins / genetics*
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Cloning, Molecular
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DNA-Binding Proteins / metabolism
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Dimerization
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Disulfides / chemistry
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Gene Expression Regulation / genetics
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Humans
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Intracellular Signaling Peptides and Proteins
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Jurkat Cells
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Lymphocyte Activation
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / genetics*
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Membrane Proteins / chemistry
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Membrane Proteins / genetics*
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Molecular Sequence Data
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NFATC Transcription Factors
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Nuclear Proteins*
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Phorbol Esters / pharmacology
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Phosphorylation
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases / metabolism*
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RNA, Messenger / metabolism
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Receptors, Antigen, T-Cell / metabolism
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SH2 Domain-Containing Protein Tyrosine Phosphatases
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Sequence Alignment
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Signal Transduction / genetics
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T-Lymphocytes / metabolism*
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Transcription Factors / metabolism
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src Homology Domains / genetics
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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DNA-Binding Proteins
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Disulfides
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Intracellular Signaling Peptides and Proteins
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Membrane Glycoproteins
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Membrane Proteins
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NFATC Transcription Factors
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Nuclear Proteins
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Phorbol Esters
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RNA, Messenger
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Receptors, Antigen, T-Cell
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SIT1 protein, human
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Transcription Factors
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PTPN11 protein, human
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PTPN6 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases
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SH2 Domain-Containing Protein Tyrosine Phosphatases
Associated data
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GENBANK/AJ010059
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GENBANK/AJ236881