Involvement of SHP-1 Tyrosine Phosphatase in TCR-mediated Signaling Pathways in Lipid Rafts

Immunity. 2001 Jun;14(6):669-80. doi: 10.1016/s1074-7613(01)00146-7.

Abstract

To elucidate the process of TCR-mediated signaling pathways in lipid rafts, we constructed a chimeric molecule that localizes activated SHP-1 to rafts. Raft targeting of activated SHP-1 in Jurkat-derived transfectants completely inhibited the expression of CD69 and transcriptional factors after TCR cross-linking. Whereas the inducible tyrosine phosphorylation of TCR zeta and ZAP-70 and the kinase activity of Lck were intact, phosphorylated LAT was rapidly dephosphorylated by raft targeting of activated SHP-1, leading to defects in LAT activation and subsequent downstream signaling events. Intriguingly, recruitment of endogenous SHP-1 to rafts and its association with LAT were dramatically increased after TCR engagement, suggesting that SHP-1 is involved in raft-mediated T cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Binding Sites
  • Calcium / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism
  • Enzyme Activation
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Jurkat Cells
  • Lymphocyte Activation / immunology
  • Membrane Microdomains / immunology*
  • Membrane Proteins / immunology*
  • Palmitates / metabolism
  • Phosphoproteins / genetics
  • Phosphoproteins / immunology
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / immunology*
  • Protein Tyrosine Phosphatases / metabolism
  • Receptors, Antigen, T-Cell / immunology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology
  • Transfection
  • Tyrosine / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • LAT protein, human
  • Membrane Proteins
  • Palmitates
  • Phosphoproteins
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins
  • antigen T cell receptor, zeta chain
  • Tyrosine
  • PTPN11 protein, human
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • Calcium