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Molecular and Cellular Biology, December 1998, p. 7130-7138, Vol. 18, No. 12
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Neutrophils Stimulated with a Variety of Chemoattractants Exhibit
Rapid Activation of p21-Activated Kinases (Paks): Separate Signals
Are Required for Activation and Inactivation of Paks
RiYun
Huang,1
Jian P.
Lian,2
Dwight
Robinson,1 and
John A.
Badwey2,3,*
Arthritis Unit, Massachusetts General
Hospital,1
Department of Biological
Chemistry and Molecular Pharmacology, Harvard Medical
School,3 and
Boston Biomedical Research
Institute,2 Boston, Massachusetts 02114
Received 25 June 1998/Returned for modification 21 July
1998/Accepted 14 September 1998
Activation of the p21-activated protein kinases (Paks) was compared
in neutrophils stimulated with a wide variety of agonists that bind to
receptors coupled to heterotrimeric G proteins. Neutrophils stimulated
with sulfatide, a ligand for the L-selectin receptor, or the
chemoattractant fMet-Leu-Phe (fMLP), platelet-activating factor,
leukotriene B4, interleukin-8, or the chemokine RANTES exhibited a rapid and transient activation of the 63- and 69-kDa Paks.
These kinases exhibited maximal activation with each of these agonists
within 15 s followed by significant inactivation at 3 min. In
contrast, neutrophils treated with the chemoattractant and
anaphylatoxin C5a exhibited a prolonged activation (>15 min) of these
Paks even though the receptor for this ligand may activate the same
overall population of complex G proteins as the fMLP receptor. Addition
of fMLP to neutrophils already stimulated with C5a resulted in the
inactivation of the 63- and 69-kDa Paks. Optimal activation of Paks
could be observed at concentrations of these agonists that elicited
only shape changes and chemotaxis in neutrophils. While all of the
agonists listed above triggered quantitatively similar activation of
the 63- and 69-kDa Paks, fMLP was far superior to the other stimuli in
triggering activation of the c-Jun N-terminal kinase (JNK) and the p38
mitogen-activated protein kinase (MAPK). These data indicate that
separate signals are required for activation and inactivation of Paks
and that, in contrast to other cell types, activated Pak does not
trigger activation of JNK or p38-MAPK in neutrophils. These results are
consistent with the recent hypothesis that G-protein-coupled receptors
may initiate signals independent of those transmitted by the
and

subunits of complex G proteins.
*
Corresponding author. Mailing address: Boston
Biomedical Research Institute, 20 Staniford St., Boston, MA 02114. Phone: (617) 742-2010, ext. 309. Fax: (617) 523-6649. E-mail:
badwey{at}disperri.bbri.harvard.edu.
Molecular and Cellular Biology, December 1998, p. 7130-7138, Vol. 18, No. 12
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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