Interaction of SLP adaptors with the SH2 domain of Tec family kinases

Eur J Immunol. 1999 Nov;29(11):3702-11. doi: 10.1002/(SICI)1521-4141(199911)29:11<3702::AID-IMMU3702>3.0.CO;2-R.

Abstract

Activation of lymphocytes through their antigen receptors leads to mobilization of intracellular Ca(2+) ions. This process requires expression of SLP adaptors and involves phosphorylation of phospholipase C-gamma isoforms by the Tec-related protein tyrosine kinase Btk in B cells and Itk in T cells. The SH2 domain of Btk and Itk is essential for phospholipase C-gamma phosphorylation and mutations in this domain lead to the X-linked agammaglobulinemia immuno deficiency in humans. Here we show that, in contrast to SH2 domains from other signaling proteins, the Btk and Itk SH2 domains exhibit a restricted binding specificity. They bind selectively to tyrosine-phosphorylated SLP-65 and SLP-76 in activated B and T cells, respectively. Our findings suggest that Btk/Itk and phospholipase C-gamma both bind via their SH2 domain to phosphorylated SLP adaptors, and that this association is required for the activation of phospholipase C-gamma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Agammaglobulinaemia Tyrosine Kinase
  • B-Lymphocytes / metabolism*
  • Carrier Proteins*
  • Cell Line
  • Glutathione Transferase / metabolism
  • Humans
  • Jurkat Cells
  • Phosphoproteins / isolation & purification
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein-Tyrosine Kinases / isolation & purification
  • Protein-Tyrosine Kinases / metabolism*
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptors, Antigen, B-Cell / metabolism*
  • Receptors, Immunologic
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction*
  • Tyrosine / metabolism
  • src Homology Domains*

Substances

  • Adaptor Proteins, Signal Transducing
  • B cell linker protein
  • Carrier Proteins
  • Phosphoproteins
  • Receptors, Antigen, B-Cell
  • Receptors, Immunologic
  • Recombinant Fusion Proteins
  • SLP-76 signal Transducing adaptor proteins
  • Tyrosine
  • Glutathione Transferase
  • LTK protein, human
  • Protein-Tyrosine Kinases
  • Receptor Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human