Interaction between Sam68 and Src family tyrosine kinases, Fyn and Lck, in T cell receptor signaling

J Biol Chem. 1997 Mar 7;272(10):6214-9. doi: 10.1074/jbc.272.10.6214.

Abstract

The Src family protein-tyrosine kinase, Fyn, is associated with the T cell receptor (TCR) and plays an important role in TCR-mediated signaling. We found that a human T cell leukemia virus type 1-infected T cell line, Hayai, overexpressed Fyn. To identify the molecules downstream of Fyn, we analyzed the tyrosine phosphorylation of cellular proteins in the cells. In Hayai, a 68-kDa protein was constitutively tyrosine-phosphorylated. The 68-kDa protein was coimmunoprecipitated with various signaling proteins such as phospholipase C gamma1, the phosphatidylinositol 3-kinase p85 subunit, Grb2, SHP-1, Cbl, and Jak3, implying that the protein might function as an adapter. Purification and microsequencing of this protein revealed that it was the RNA-binding protein, Sam68 (Src associated in mitosis, 68 kDa). Sam68 was associated with the Src homology 2 and 3 domains of Fyn and also those of another Src family kinase, Lck. CD3 cross-linking induced tyrosine phosphorylation of Sam68 in uninfected T cells. These data suggest that Sam68 participates in the signal transduction pathway downstream of TCR-coupled Src family kinases Fyn and Lck in lymphocytes, that is not only in the mitotic pathway downstream of c-Src in fibroblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Cell Line
  • GRB2 Adaptor Protein
  • HTLV-I Infections / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Mitosis
  • Phosphotyrosine / metabolism
  • Protein Binding
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Proteins / metabolism
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-fyn
  • Proto-Oncogene Proteins pp60(c-src) / physiology
  • RNA-Binding Proteins / physiology*
  • Receptors, Antigen, T-Cell / physiology*
  • Signal Transduction
  • ZAP-70 Protein-Tyrosine Kinase

Substances

  • Adaptor Proteins, Signal Transducing
  • GRB2 Adaptor Protein
  • GRB2 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • RNA-Binding Proteins
  • Receptors, Antigen, T-Cell
  • Phosphotyrosine
  • Protein-Tyrosine Kinases
  • FYN protein, human
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Proto-Oncogene Proteins c-fyn
  • Proto-Oncogene Proteins pp60(c-src)
  • ZAP-70 Protein-Tyrosine Kinase
  • ZAP70 protein, human
  • PTPN11 protein, human
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases