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J. Biol. Chem., Vol. 278, Issue 12, 10657-10667, March 21, 2003
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From the Here we report cellular arachidonate (AA) release
and prostaglandin (PG) production by novel classes of secretory
phospholipase A2s (sPLA2s), groups III
and XII. Human group III sPLA2 promoted spontaneous AA
release, which was augmented by interleukin-1, in HEK293 transfectants.
The central sPLA2 domain alone was sufficient for its
in vitro enzymatic activity and for cellular AA release at
the plasma membrane, whereas either the unique N- or C-terminal domain
was required for heparanoid-dependent action on cells to augment AA release, cyclooxygenase-2 induction, and PG production. Group III sPLA2 was constitutively expressed in two human
cell lines, in which other sPLA2s exhibited different
stimulus inducibility. Human group XII sPLA2 had a weak
enzymatic activity in vitro and minimally affects cellular
AA release and PG production. Cells transfected with group XII
sPLA2 exhibited abnormal morphology, suggesting a unique
functional aspect of this enzyme. Based on the present results as well
as our current analyses on the group I/II/V/X sPLA2s,
general properties of cellular actions of a full set of mammalian
sPLA2s in regulating AA metabolism are discussed.
Cellular Arachidonate-releasing Function of Novel
Classes of Secretory Phospholipase A2s (Groups III and
XII)*
§,,,
,,,,,, and
Department of Health Chemistry, School of
Pharmaceutical Sciences, and the ¶ First Department of Internal
Medicine, School of Medicine, Showa University, 1-5-8 Hatanodai,
Shinagawa-ku, Tokyo 142-8555, Japan, the ** Departments of
Chemistry and Biochemistry, University of Washington, Seattle,
Washington 98195-1700, and the Institut de Pharmacologie
Moleculaire et Cellulaire, CNRS-UPR 411, 660 route des Lucioles, Sophia
Antipolis, 06560 Valbonne, France
*
This work was supported by grants-in-aid for scientific
research from the Ministry of Education, Science, Culture, Sports, and
Technology of Japan.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.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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