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IL‐5‐induced integrin adhesion of human eosinophils caused by ERK1/2‐mediated activation of cPLA 2
Author(s) -
Zhu Xiangdong,
Jacobs Benjamin,
Boetticher Evan,
Myou Shigeharu,
Meliton Angelo,
Sano Hiroyuki,
Lambertino Anissa T.,
Muñoz Nilda M.,
Leff Alan R.
Publication year - 2002
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 - 10.1189/jlb.72.5.1046
Subject(s) - proto oncogene tyrosine protein kinase src , tyrosine phosphorylation , lyn , tyrosine protein kinase csk , microbiology and biotechnology , biology , tyrosine kinase , mitogen activated protein kinase kinase , map kinase kinase kinase , map2k7 , cancer research , phosphorylation , mapk/erk pathway , sh2 domain , cyclin dependent kinase 2 , signal transduction , protein kinase a
We examined the mechanism by which interleukin (IL)‐5 causes β 2 ‐integrin adhesion of human eosinophils. IL‐5 caused time‐dependent activation of extracellular signal‐regulated kinases 1 and 2 (ERK1/2) and p38α in eosinophils as detected by their phosphorylation. Preincubation of eosinophils with U0126, a mitogen‐activated protein kinase/ERK kinase inhibitor, suppressed IL‐5‐induced activation of cytosolic phospholipase A 2 (cPLA 2 ) and eosinophil adhesion, and p38 inhibition by SB203580 had neither effect. ERK1/2 phosphorylation and eosinophil adhesion were blocked by inhibition of the src‐family tyrosine kinase, Janus tyrosine kinase (JAK)2, or phosphoinositide‐3 kinase (PI3K). Coimmunoprecipitation assay demonstrated that Lyn, a src‐family tyrosine kinase, was constitutively associated with PI3K. Inhibition of src‐tyrosine kinase but not JAK2 suppressed PI3K activation. Our data suggest that IL‐5 induces β 2 ‐integrin adhesion of human eosinophils by regulation of cPLA 2 activation caused by ERK1/2 phosphorylation. This phosphorylation results from activation of PI3K and protein tyrosine kinases. We also find that src‐family tyrosine kinase, possibly Lyn, is the upstream kinase causing PI3K activation.