SHP2-interacting transmembrane adaptor protein (SIT), a novel disulfide-linked dimer regulating human T cell activation

• Published in: The Journal of experimental medicine Vol. 189; no. 8; pp. 1181 - 1194
• Main Authors: Marie-Cardine, A, Kirchgessner, H, Bruyns, E, Shevchenko, A, Mann, M, Autschbach, F, Ratnofsky, S, Meuer, S, Schraven, B
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 19-04-1999
• Subjects: Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Carrier Proteins - chemistry; Carrier Proteins - genetics; Cloning, Molecular; Dimerization; Disulfides - chemistry; DNA-Binding Proteins - metabolism; Gene Expression Regulation - genetics; Humans; Intracellular Signaling Peptides and Proteins; Jurkat Cells; Lymphocyte Activation; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - genetics; Membrane Proteins - chemistry; Membrane Proteins - genetics; Molecular Sequence Data; NFATC Transcription Factors; Nuclear Proteins; Phorbol Esters - pharmacology; Phosphorylation; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Protein Tyrosine Phosphatases - metabolism; Receptors, Antigen, T-Cell - metabolism; RNA, Messenger - metabolism; Sequence Alignment; SH2 Domain-Containing Protein Tyrosine Phosphatases; Signal Transduction - genetics; src Homology Domains - genetics; T-Lymphocytes - metabolism; Transcription Factors - metabolism
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.189.8.1181

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.