Requirement of Lyn and Syk tyrosine kinases for the prevention of apoptosis by cytokines in human eosinophils

Shida Yousefi, Daniel C. Hoessli, Kurt Blaser, Gordon B. Mills, Hans Uwe Simon

    Research output: Contribution to journalArticle

    207 Scopus citations

    Abstract

    In allergic diseases, the cytokines interleukin (IL)5 and granulocyte/macrophage colony-stimulating factor (GM-CSF) are upregulated and have been proposed to cause blood and tissue eosinophilia by inhibition of eosinophil apoptosis. We demonstrate herein, in freshly isolated human eosinophils, that the IL-3/IL-5/GM-CSF receptor β subunit interacts with cytoplasmic tyrosine kinases to induce phosphorylation of several cellular substrates, including the β subunit itself. The Lyn and Syk intracellular tyrosine kinases constitutively associate at a low level with the IL-3/IL- 5/GM-CSF receptor β subunit in human eosinophils. Stimulation with GM-CSF or IL-5 results in a rapid and transient increase in the amount of Lyn and Syk associated with the IL-3/IL-5/GM-CSF receptor β subunit. Lyn is required for optimal tyrosine phosphorylation and activation of Syk. In contrast, Syk is not required for optimal tyrosine phosphorylation and activation of Lyn. These data suggest that Lyn is proximal to Syk in a tyrosine kinase cascade that transduces IL-3, IL-5, or GM-CSF signals. Compatible with this model, both Lyn and Syk are essential for the activation of the antiapoptotic pathway(s) reduced through the IL-3/IL-5/GM-CSF receptor β subunit in human eosinophils.

    Original languageEnglish (US)
    Pages (from-to)1407-1414
    Number of pages8
    JournalJournal of Experimental Medicine
    Volume183
    Issue number4
    DOIs
    StatePublished - Apr 1 1996

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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