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Vol. 273, Issue 2, 1058-1063, January 9, 1998
From the Centre de Recherche en Rhumatologie et Immunologie, Centre
de Recherche du CHUL, and Department of Medicine, Faculty of Medicine,
Laval University, Ste-Foy, Québec G1V 4G2, Canada and the
Granulocyte-macrophage colony stimulating factor
(GM-CSF) regulates many of the biological functions of human
neutrophils. This includes the stimulation of protein synthesis and the
tyrosine phosphorylation of various proteins among which is JAK2. The
present study was aimed at characterizing in detail the pattern of
activation by GM-CSF of the JAK/STAT pathway in human neutrophils. The
results obtained show that the stimulation of human neutrophils by
GM-CSF specifically led to tyrosine phosphorylation of JAK2 and had no effect on JAK1, JAK3, or TYK2. Furthermore, GM-CSF induced the tyrosine
phosphorylation of STAT3 and STAT5 but not of STAT1, STAT2, STAT4, or
STAT6. Tyrosine phosphorylation of STAT3 was transient reaching its
maximum at 15 min. STAT5 presented a different pattern of tyrosine
phosphorylation. The anti-STAT5 antibodies identified two proteins at
94 and 92 kDa. The 94-kDa STAT5 was constitutively tyrosine
phosphorylated and showed no change upon GM-CSF stimulation. On the
other hand, the 92-kDa STAT5 was tyrosine phosphorylated within 1 min
of GM-CSF treatment and this was maintained for at least 30 min. By the
use of specific antibodies, it was determined that only STAT5B, and not
STAT5A, was tyrosine phosphorylated in GM-CSF-treated neutrophils.
Furthermore, GM-CSF treatment induced an increase in the ability of
STAT3 and STAT5B, but not STAT5A, to bind DNA probes. The specificity
of the pattern of activation of the JAK/STAT pathway suggests that it
may be directly linked to the modulation of the functions of mature
nondividing, human neutrophils by GM-CSF.
Granulocyte-Macrophage Colony-stimulating Factor-activated
Signaling Pathways in Human Neutrophils
SELECTIVE ACTIVATION OF Jak2, Stat3, AND Stat5B
, and Laboratory of Immunogenetics, NIAID, National Institutes
of Health, Bethesda, Maryland 20852
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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