Lyn tyrosine kinase is important for IL-5-stimulated eosinophil differentiation

Susan Stafford, Clifford Lowell, Sanjiv Sur, Rafeul Alam

Research output: Contribution to journalArticle

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Abstract

IL-5 plays a pivotal role in growth and differentiation of eosinophils. The signal transduction mechanism of IL-5Rα is largely unknown. We have demonstrated that IL-5 induces tyrosine phosphorylation of IL-5Rα in eosinophils. To identify IL-5Rα-associated tyrosine kinases, we have examined the expression of Src family tyrosine kinases in eosinophils. Among the Src family members, Lyn, Hck, Fgr, and Lck are present in eosinophils, and, among these four kinases, only Lyn is associated with the IL-5Rα under basal conditions. We also confirm the association of Janus kinase (Jak)2 with IL-5Rα. Lyn kinase phosphorylates both IL-5Rα and βcR in vitro. The importance of Lyn kinase for eosinophil differentiation was studied using antisense oligodeoxynucleotides. Lyn antisense oligodeoxynucleotide blocks eosinophil differentiation from stem cells in a dose-dependent manner. The Jak2 inhibitor tyrphostin AG490 also inhibits eosinophil differentiation. The importance of Lyn for eosinophil differentiation was further studied using Lyn knockout mice. The IL-5-stimulated eosinophil differentiation from bone marrow cells is significantly inhibited in Lyn-/- mice as compared with that in control mice. We conclude that both Lyn and Jak2 play an essential role in IL-5Rα signaling, leading to eosinophil differentiation. The effect of Lyn appears to be relatively specific for the eosinophilic lineage.

Original languageEnglish (US)
Pages (from-to)1978-1983
Number of pages6
JournalJournal of Immunology
Volume168
Issue number4
StatePublished - Feb 15 2002

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Interleukin-5
Eosinophils
Protein-Tyrosine Kinases
Phosphotransferases
Oligodeoxyribonucleotides
Janus Kinase 2
Tyrphostins
src-Family Kinases
Knockout Mice
Bone Marrow Cells
Tyrosine
Signal Transduction
Stem Cells
Phosphorylation

ASJC Scopus subject areas

  • Immunology

Cite this

Stafford, S., Lowell, C., Sur, S., & Alam, R. (2002). Lyn tyrosine kinase is important for IL-5-stimulated eosinophil differentiation. Journal of Immunology, 168(4), 1978-1983.

Lyn tyrosine kinase is important for IL-5-stimulated eosinophil differentiation. / Stafford, Susan; Lowell, Clifford; Sur, Sanjiv; Alam, Rafeul.

In: Journal of Immunology, Vol. 168, No. 4, 15.02.2002, p. 1978-1983.

Research output: Contribution to journalArticle

Stafford, S, Lowell, C, Sur, S & Alam, R 2002, 'Lyn tyrosine kinase is important for IL-5-stimulated eosinophil differentiation', Journal of Immunology, vol. 168, no. 4, pp. 1978-1983.
Stafford S, Lowell C, Sur S, Alam R. Lyn tyrosine kinase is important for IL-5-stimulated eosinophil differentiation. Journal of Immunology. 2002 Feb 15;168(4):1978-1983.
Stafford, Susan ; Lowell, Clifford ; Sur, Sanjiv ; Alam, Rafeul. / Lyn tyrosine kinase is important for IL-5-stimulated eosinophil differentiation. In: Journal of Immunology. 2002 ; Vol. 168, No. 4. pp. 1978-1983.
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AB - IL-5 plays a pivotal role in growth and differentiation of eosinophils. The signal transduction mechanism of IL-5Rα is largely unknown. We have demonstrated that IL-5 induces tyrosine phosphorylation of IL-5Rα in eosinophils. To identify IL-5Rα-associated tyrosine kinases, we have examined the expression of Src family tyrosine kinases in eosinophils. Among the Src family members, Lyn, Hck, Fgr, and Lck are present in eosinophils, and, among these four kinases, only Lyn is associated with the IL-5Rα under basal conditions. We also confirm the association of Janus kinase (Jak)2 with IL-5Rα. Lyn kinase phosphorylates both IL-5Rα and βcR in vitro. The importance of Lyn kinase for eosinophil differentiation was studied using antisense oligodeoxynucleotides. Lyn antisense oligodeoxynucleotide blocks eosinophil differentiation from stem cells in a dose-dependent manner. The Jak2 inhibitor tyrphostin AG490 also inhibits eosinophil differentiation. The importance of Lyn for eosinophil differentiation was further studied using Lyn knockout mice. The IL-5-stimulated eosinophil differentiation from bone marrow cells is significantly inhibited in Lyn-/- mice as compared with that in control mice. We conclude that both Lyn and Jak2 play an essential role in IL-5Rα signaling, leading to eosinophil differentiation. The effect of Lyn appears to be relatively specific for the eosinophilic lineage.

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