SHP2-interacting transmembrane adaptor protein (SIT), a novel disulfide-linked dimer regulating human T cell activation.
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.
Mesh Terms:
Amino Acid Sequence, Carrier Proteins, Cloning, Molecular, DNA-Binding Proteins, Dimerization, Disulfides, Gene Expression Regulation, Humans, Intracellular Signaling Peptides and Proteins, Jurkat Cells, Lymphocyte Activation, Membrane Glycoproteins, Membrane Proteins, Molecular Sequence Data, NFATC Transcription Factors, Nuclear Proteins, Phorbol Esters, Phosphorylation, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, RNA, Messenger, Receptors, Antigen, T-Cell, SH2 Domain-Containing Protein Tyrosine Phosphatases, Sequence Alignment, Signal Transduction, T-Lymphocytes, Transcription Factors, src Homology Domains
Amino Acid Sequence, Carrier Proteins, Cloning, Molecular, DNA-Binding Proteins, Dimerization, Disulfides, Gene Expression Regulation, Humans, Intracellular Signaling Peptides and Proteins, Jurkat Cells, Lymphocyte Activation, Membrane Glycoproteins, Membrane Proteins, Molecular Sequence Data, NFATC Transcription Factors, Nuclear Proteins, Phorbol Esters, Phosphorylation, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, RNA, Messenger, Receptors, Antigen, T-Cell, SH2 Domain-Containing Protein Tyrosine Phosphatases, Sequence Alignment, Signal Transduction, T-Lymphocytes, Transcription Factors, src Homology Domains
J. Exp. Med.
Date: Apr. 19, 1999
PubMed ID: 10209036
View in: Pubmed Google Scholar
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