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Src kinases regulate PKB activation and modulate cytokine and chemoattractant‐controlled neutrophil functioning
Author(s) -
Nijhuis Evert,
Lammers JanWillem J,
Koenderman Leo,
Coffer Paul J.
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.71.1.115
Subject(s) - proto oncogene tyrosine protein kinase src , kinase , phosphorylation , biology , microbiology and biotechnology , tyrosine phosphorylation , tyrosine kinase , receptor tyrosine kinase , protein kinase b , ly294002 , cancer research , signal transduction
Tyrosine phosphorylation is thought to be critical in the regulation of neutrophil functioning, and members of the Src family of tyrosine kinases have recently been shown to be regulated in activated granulocytes. We have used a specific pharmacological inhibitor of Src kinases, pyrazolpyrimidine 1 (PP1), to evaluate the role of Src kinases in cytokine/chemoattractant‐induced regulation of neutrophil function. PP1 inhibits PKB phosphorylation but not STAT5 phosphorylation or the activation of MAP kinases by fMLP or GM‐CSF. Pretreatment of neutrophils with PP1 and with the PI3K inhibitor LY294002 resulted in a strong inhibition of fMLP‐induced superoxide production and cytokine‐mediated survival but not fMLP‐induced migration. It is interesting that the kinetics of inhibition of actin polymerization and the respiratory burst are very similar. Although initiation of both processes was not affected, sustained activation was inhibited by PP1. Taken together, our results demonstrate a critical role for Src kinases in regulating neutrophil cytotoxic‐effector functioning through PI3K‐PKB.