Lyn, Jak2, and Raf-1 kinases are critical for the antiapoptotic effect of interleukin 5, whereas only Raf-1 kinase is essential for eosinophil activation and degranulation

Konrad Pazdrak, Barbara Olszewska-Pazdrak, Susan Stafford, Roberto Garofalo, Rafeul Alam

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Interleukin (IL)-5 has been shown to activate many signaling molecules in eosinophils, but their functional relevance remains unknown. We have examined the functional relevance of Lyn, Jak2, and Raf-1 kinases in eosinophil survival, upregulation of adhesion molecules and degranulation. To this goal we used Lyn and Raf-1 antisense (AS) oligodeoxynucleotides (ODN) to inhibit the expression of these proteins and tyrphostin AG490 to specifically block the activation of Jak2. We have demonstrated that all three kinases are important for IL-5-induced suppression of eosinophil apoptosis. However, Lyn and Jak2 tyrosine kinases are not important for the upregulation of CD11b and the secretion of eosinophil cationic protein. In contrast, Raf-1 kinase is critical for both these functions. This is the first identification of specific signaling molecules responsible for three important functions of eosinophils. We have established a central role for Raf-1 kinase in regulating eosinophil survival, expression of β2 integrins and degranulation. Further, there appears to be a dissociation between two receptor-associated tyrosine kinases, i.e., Lyn and Jak2, and the activation of Raf-1 kinase. The delineation of the functional relevance of signaling molecules will help design therapeutic approaches targeting specific eosinophil function.

Original languageEnglish (US)
Pages (from-to)421-429
Number of pages9
JournalJournal of Experimental Medicine
Volume188
Issue number3
DOIs
StatePublished - Aug 3 1998

Fingerprint

Proto-Oncogene Proteins c-raf
Interleukin-5
Eosinophils
Up-Regulation
Tyrphostins
Eosinophil Cationic Protein
Oligodeoxyribonucleotides
Receptor Protein-Tyrosine Kinases
Integrins
Protein-Tyrosine Kinases
Phosphotransferases
Apoptosis

Keywords

  • Degranulation
  • Eosinophil
  • Interleukin 5
  • Raf-1 kinase
  • Signal transduction

ASJC Scopus subject areas

  • Immunology

Cite this

Lyn, Jak2, and Raf-1 kinases are critical for the antiapoptotic effect of interleukin 5, whereas only Raf-1 kinase is essential for eosinophil activation and degranulation. / Pazdrak, Konrad; Olszewska-Pazdrak, Barbara; Stafford, Susan; Garofalo, Roberto; Alam, Rafeul.

In: Journal of Experimental Medicine, Vol. 188, No. 3, 03.08.1998, p. 421-429.

Research output: Contribution to journalArticle

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