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 Mills, Hans Uwe Simon

Research output: Contribution to journalArticle

204 Citations (Scopus)

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
Externally publishedYes

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Interleukin-5
Eosinophils
Protein-Tyrosine Kinases
Granulocyte-Macrophage Colony-Stimulating Factor Receptors
Interleukin-3
Apoptosis
Cytokines
Granulocyte-Macrophage Colony-Stimulating Factor
Phosphorylation
Tyrosine
Eosinophilia
Syk Kinase

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Requirement of Lyn and Syk tyrosine kinases for the prevention of apoptosis by cytokines in human eosinophils. / Yousefi, Shida; Hoessli, Daniel C.; Blaser, Kurt; Mills, Gordon; Simon, Hans Uwe.

In: Journal of Experimental Medicine, Vol. 183, No. 4, 01.04.1996, p. 1407-1414.

Research output: Contribution to journalArticle

Yousefi, Shida ; Hoessli, Daniel C. ; Blaser, Kurt ; Mills, Gordon ; Simon, Hans Uwe. / Requirement of Lyn and Syk tyrosine kinases for the prevention of apoptosis by cytokines in human eosinophils. In: Journal of Experimental Medicine. 1996 ; Vol. 183, No. 4. pp. 1407-1414.
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AB - 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.

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