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*
Department of Internal Medicine, Division of Allergy and Immunology, University of Texas Medical Branch, Galveston, TX 77555; and
Department of Laboratory Medicine, University of California, San Francisco, CA 94143
IL-5 plays a pivotal role in growth and differentiation of
eosinophils. The signal transduction mechanism of IL-5R
is largely
unknown. We have demonstrated that IL-5 induces tyrosine
phosphorylation of IL-5R in eosinophils. To identify
IL-5R-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-5R under
basal conditions. We also confirm the association of Janus kinase
(Jak)2 with IL-5R. Lyn kinase phosphorylates both IL-5R and 
cR
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-5R signaling, leading to eosinophil
differentiation. The effect of Lyn appears to be relatively specific
for the eosinophilic lineage.
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