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J. Biol. Chem., Vol. 277, Issue 24, 21537-21541, June 14, 2002
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From the Canadian Institutes for Health Research Group on the
Molecular Mechanisms of Inflammation, Centre de recherche en
rhumatologie et immunologie, Centre de recherche du Centre Hospitalier
de l'Université Laval, Department of Medicine, Laval University,
Québec G1V 4G2, Canada
The importance of the tyrosine phosphorylation
cascades in the initiation and regulation of the functional
responsiveness of human neutrophils is well established. On the other
hand, the link between the G protein-coupled receptors (to which the
receptors for chemotactic factors belong) and the activation of
tyrosine kinases is very poorly characterized. Based on previous
observations indicating that the stimulation of tyrosine
phosphorylation was sensitive to inhibition by the phosphatidylinositol
3-kinase inhibitor wortmannin and the recent description of
pleckstrin homology domain-containing tyrosine kinases (the Tec
family), we have examined the potential implication of the latter in
the responses of human neutrophils to chemotactic factors. The results
obtained indicate firstly that several members of the Tec family of
tyrosine kinases are expressed in human neutrophils, including Tec,
Btk, and Bmx. Stimulation of the cells with fMet-Leu-Phe led to a rapid
activation of Tec as indicated by its translocation to a membrane
fraction and to increases in its in situ level of tyrosine
phosphorylation and its capacity to tyrosine phosphorylate itself or an
exogenous substrate (SAM68-GST) in in vitro kinase assays.
The activation of Tec was inhibited by pertussis toxin as well as by
wortmannin. The results of this study provide direct evidence for the
implication of Tec family kinases in the responses of human neutrophils
to chemotactic factors. They also suggest that one of the links between G protein-coupled receptors and tyrosine kinases depends on the activation of phosphatidylinositol 3-kinase and the generation of
phosphatidylinositol 3,4,5-trisphosphate.
Chemotactic Factor-induced Recruitment and Activation of Tec
Family Kinases in Human Neutrophils
IMPLICATION OF PHOSPHATIDYLINOSITOL 3-KINASES*
*
This work was supported in part by grants from the Canadian
Institutes for Health Research.The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: CHUL du CHUQ, Room T
1-49, 2705 Blvd. Laurier, Québec, Québec G1V 4G2, Canada. Tel: 418-654-2772; Fax: 418-654-2765; E-mail:
paul.naccache@crchul. ulaval.ca.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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