SWAP-70-like adapter of T cells, an adapter protein that regulates early TCR-initiated signaling in Th2 lineage cells

Immunity. 2003 Mar;18(3):403-14. doi: 10.1016/s1074-7613(03)00054-2.

Abstract

We describe the isolation of a protein, SWAP-70-like adapter of T cells (SLAT), which is expressed at high levels in thymocytes and differentiated Th2 cells. SLAT expression was upregulated in differentiating Th2 cells and downregulated in Th1 cells. Ectopic SLAT expression exerted positive or negative effects on IL-4 versus IFNgamma induction, respectively. TCR signaling induced translocation of SLAT to the immunological synapse and its association with ZAP-70 kinase. SLAT reduced the association of ZAP-70 with TCR-zeta and interfered with ZAP-70 but not Lck signaling. Consistent with these results, pharmacological inhibition of ZAP-70 also induced Th2 skewing. Thus, SLAT is a protein which plays a role in Th2 development and/or activation, perhaps by interfering with ZAP-70 signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biological Transport, Active
  • Cell Differentiation / drug effects
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology*
  • DNA-Binding Proteins / isolation & purification
  • Enzyme Inhibitors / pharmacology
  • Genes, T-Cell Receptor
  • Guanine Nucleotide Exchange Factors*
  • Mice
  • Mice, Transgenic
  • Minor Histocompatibility Antigens
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / immunology*
  • Nuclear Proteins / isolation & purification
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptors, Antigen, T-Cell / metabolism*
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Stilbenes / pharmacology
  • Th2 Cells / cytology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*
  • ZAP-70 Protein-Tyrosine Kinase

Substances

  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Guanine Nucleotide Exchange Factors
  • Minor Histocompatibility Antigens
  • Nuclear Proteins
  • Receptors, Antigen, T-Cell
  • SLAT protein, mouse
  • Stilbenes
  • Swap70 protein, mouse
  • 3,3',4,5'-tetrahydroxystilbene
  • Protein-Tyrosine Kinases
  • ZAP-70 Protein-Tyrosine Kinase
  • Zap70 protein, mouse

Associated data

  • GENBANK/AF329497