Multiple roles played by Src family tyrosine kinases in TCR signal transduction

Makio Iwashima, Sho Yamasaki, Yi Ying Hnang, Shinobu Mitsuda, Masako Takamatsu

    Research output: Contribution to journalArticle

    Abstract

    Research and Development Corporation and Pharmaceuticals Laboratory II, Life Science Research Sector, Mitsubishi Chemical Corporation Antigenic stimulation on the T cell antigen receptor (TCR) initiates signal transduction through the immunoreceptor tyrosine-based activation motifs (ITAMs). When its two tyrosines are phosphorylated, ITAM forms a binding site for Z:\P-70, one of the cytoplasmic protein tyrosine kinases essential for T cell activation. Lck appears to be a dominant kinase that phosphorylates tyrosines in ITAMs but Fyn also plays the equivalent role to Lck when T cells are stimulated by super antigens. The signaling process that follows ZAP-70 binding to ITAM has been analyzed by the construction of fusion proteins that localize ZAP-70 to the plasma membrane. We found that membrane-localized forms of chimeric ZAP-70 proteins induce late signaling events such as activation of nuclear factor of activated T-cells (NF-AT) without any stimulation. This activity was observed only when Lck was expressed and functional. Each mutation that affects the function of Lck in the kinase, Src-homology 2 (SH2) and Src-homology 3 (SII3) domains greatly impaired the signaling ability of the chimeric protein. Among the SH3 domain binding proteins, we identified a molecule that is a substrate for ZAP-70. TCR stimulation also induces tyrosino phosphorylation of the molecule. This indicates that the Stt3 domain of Lck may flmction as an adaptor to bring the substrate for ZAP-70 into the TCR complex for tyrosine phosphorylation by ZAP-70 and induction of downstream signaling events.

    Original languageEnglish
    Pages (from-to)A1058
    JournalFASEB Journal
    Volume11
    Issue number9
    Publication statusPublished - Dec 1 1997

    All Science Journal Classification (ASJC) codes

    • Biotechnology
    • Biochemistry
    • Molecular Biology
    • Genetics

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  • Cite this

    Iwashima, M., Yamasaki, S., Hnang, Y. Y., Mitsuda, S., & Takamatsu, M. (1997). Multiple roles played by Src family tyrosine kinases in TCR signal transduction. FASEB Journal, 11(9), A1058.