Blockage of chemotactic peptide-induced stimulation of neutrophils by wortmannin as a result of selective inhibition of phosphatidylinositol 3-kinase.
Year: 1994
Type: article
Abstract: Wortmannin, a fungal metabolite, inhibited 32P labeling of phosphatidylinositol trisphosphate, a product of phosphatidylinositol 3-kinase (PI 3-kinase), selectively in formyl peptide-stimulated 32P-loaded guinea pig neutrophils. The inhibition was of the same concentration dependence (with the half-maximal inhibition around 50 nM) as was observed for the simultaneous inhibition of formyl peptide-induced superoxide anion production. Wortmannin inhibited all three of the PI 3-kinase activities found in the cytosol fraction of guinea pig neutrophils, with a similar dose dependence (the half-maximal effects at 5 nM). Wortmannin was also effective on an immunologically purified preparation of the enzyme. The inhibition was of a noncompetitive type with regard to ATP and was observed consistently when PI, PI monophosphate, or PI bisphosphate was used as substrate. PI 4-kinase activity was not affected. It is concluded, therefore, that wortmannin abolished the formyl peptide-induced stimulation of neutrophils as a result of the inhibition of PI 3-kinase. An essential role of PI 3-kinase in receptor-mediated signaling in neutrophils thus evidenced with the use of wortmannin will be expanded to other cellular signaling systems.
Source: Journal of Biological Chemistry
Authors: T. Okada, L. Sakuma, Y. Fukui, O. Hazeki, M. Ui
Institution: The University of Tokyo
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1528368632