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MBC in Press, published online ahead of print December 4, 2006
Mol. Biol. Cell 10.1091/mbc.E06-05-0418

A more recent version of this article appeared on February 1, 2007 Originally published as MBC in Press, 10.1091/mbc.E06-05-0418 on November 29, 2006
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Submitted on May 16, 2006
Revised on November 15, 2006
Accepted on November 21, 2006

A Chemoattractant-mediated Gi-coupled Pathway Activates Adenylyl Cyclase in Human Neutrophils

Dana C. Mahadeo, Mirkka Janka-Junttila, Rory L. Smoot, Pavla Roselova, and Carole A. Parent

Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4256

Monitoring Editor: John York

Neutrophils and Dictyostelium use conserved signal transduction pathways to decipher chemoattractant gradients and migrate directionally. In both cell types, addition of chemoattractants stimulates the production of cAMP, which has been suggested to regulate chemotaxis. We set out to define the mechanism by which chemoattractants increase cAMP levels in human neutrophils. We show that chemoattractants elicit a rapid and transient activation of adenylyl cyclase (AC). This activation is sensitive to pertussis toxin treatment but independent of PI3K activity and an intact cytoskeleton. Remarkably, and in sharp contrast to G{alpha}s-mediated activation, chemoattractant-induced AC activation is lost in cell lysates. Of the nine, differentially regulated, transmembrane AC isoforms in the human genome, we find that isoforms III, IV, VII, and IX are expressed in human neutrophils. We conclude that the signal transduction cascade used by chemoattractants to activate AC is conserved in Dictyostelium and human neutrophils, and is markedly different from the canonical G{alpha}s-meditated pathway.


Address correspondence to: Carole A. Parent (parentc{at}helix.nih.gov)




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J. Leukoc. Biol.Home page
R. E. Eckert and S. L. Jones
Regulation of VASP serine 157 phosphorylation in human neutrophils after stimulation by a chemoattractant
J. Leukoc. Biol., November 1, 2007; 82(5): 1311 - 1321.
[Abstract] [Full Text] [PDF]




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