Interaction between Sam68 and Src family tyrosine kinases, Fyn and Lck, in T cell receptor signaling.
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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Cell Line, GRB2 Adaptor Protein, HTLV-I Infections, Humans, Intracellular Signaling Peptides and Proteins, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Mitosis, Phosphotyrosine, 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, Protein-Tyrosine Kinases, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-fyn, Proto-Oncogene Proteins pp60(c-src), RNA-Binding Proteins, Receptors, Antigen, T-Cell, Signal Transduction, ZAP-70 Protein-Tyrosine Kinase
Adaptor Proteins, Signal Transducing, Cell Line, GRB2 Adaptor Protein, HTLV-I Infections, Humans, Intracellular Signaling Peptides and Proteins, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Mitosis, Phosphotyrosine, 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, Protein-Tyrosine Kinases, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-fyn, Proto-Oncogene Proteins pp60(c-src), RNA-Binding Proteins, Receptors, Antigen, T-Cell, Signal Transduction, ZAP-70 Protein-Tyrosine Kinase
J. Biol. Chem.
Date: Mar. 07, 1997
PubMed ID: 9045636
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