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

J Exp Med. 1999 Apr 19;189(8):1181-94. doi: 10.1084/jem.189.8.1181.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Cloning, Molecular
  • DNA-Binding Proteins / metabolism
  • Dimerization
  • Disulfides / chemistry
  • 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*
  • RNA, Messenger / metabolism
  • Receptors, Antigen, T-Cell / metabolism
  • SH2 Domain-Containing Protein Tyrosine Phosphatases
  • Sequence Alignment
  • Signal Transduction / genetics
  • T-Lymphocytes / metabolism*
  • Transcription Factors / metabolism
  • src Homology Domains / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA-Binding Proteins
  • Disulfides
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Phorbol Esters
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • SIT1 protein, human
  • Transcription Factors
  • PTPN11 protein, human
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • SH2 Domain-Containing Protein Tyrosine Phosphatases

Associated data

  • GENBANK/AJ010059
  • GENBANK/AJ236881