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Involvement of JAK2, but not PI 3‐kinase/Akt and MAP kinase pathways, in anti‐apoptotic signals of GM‐CSF in human eosinophils
Author(s) -
Miike Satoshi,
Nakao Atsuhito,
Hiraguri Masaki,
Kurasawa Kazuhiro,
Saito Yasushi,
Iwamoto Itsuo
Publication year - 1999
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.65.5.700
Subject(s) - wortmannin , ly294002 , protein kinase b , biology , kinase , ask1 , map kinase kinase kinase , mitogen activated protein kinase kinase , mitogen activated protein kinase , microbiology and biotechnology , cancer research , mapk/erk pathway , signal transduction , protein kinase a
Abstract Granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) transmits anti‐apoptotic signals in eosinophils and is involved in tissue eosinophilia at the site of allergic inflammation. We determined whether phosphatidylinositol 3‐kinase (PI 3‐kinase) and mitogen‐activated protein kinase (MAP kinase) are involved in anti‐apoptotic signals of GM‐CSF in eosinophils. GM‐CSF phosphorylated Akt, a downstream component of PI 3‐kinase, and MAP kinases (ERK1 and ERK2) at 10 min after stimulation in eosinophils. GM‐CSF prevented eosinophil apoptosis and sustained its survival during the 5‐day culture. However, neither two PI‐3 kinase inhibitors, wortmannin and LY294002, nor MEK inhibitor PD98059 inhibited GM‐CSF‐induced survival of eosinophils, although wortmannin and PD98059 inhibited GM‐CSF‐induced Akt phosphorylation and MAP kinase activation in eosinophils, respectively. In contrast, JAK2 inhibitor AG‐490 inhibited both GM‐CSF‐induced JAK2 phosphorylation and cell survival in eosinophils. These results indicate that activation of JAK2, but not activation of PI 3‐kinase/Akt and MAP kinase pathways, is critical for anti‐apoptotic signals of GM‐CSF in human eosinophils. Our findings suggest that manipulation of JAK2 activation would be useful for the treatment of allergic disorders. J. Leukoc. Biol. 65: 700–706; 1999.