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J. Biol. Chem., Vol. 277, Issue 52, 50683-50692, December 27, 2002
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From the Many critical cellular processes, including
proliferation, vesicle trafficking, and secretion, are regulated by
both phospholipase D (PLD) and the actin microfilament system.
Stimulation of human PLD1 results in its association with the
detergent-insoluble actin cytoskeleton, but the molecular mechanisms
and functional consequences of PLD-actin interactions remain
incompletely defined. Biochemical and pharmacologic modulation of actin
polymerization resulted in complex bidirectional effects on PLD
activity, both in vitro and in vivo. Highly
purified G-actin inhibited basal and stimulated PLD activity, whereas
F-actin produced the opposite effects. Actin-induced modulation of PLD
activity was independent of the activating stimulus. The efficacy and
potency of the effects of actin were isoform-specific but broadly
conserved among actin family members. Human
Regulation of Phospholipase D Activity by Actin
ACTIN EXERTS BIDIRECTIONAL MODULATION OF MAMMALIAN
PHOSPOLIPASE D ACTIVITY IN A POLYMERIZATION-DEPENDENT,
ISOFORM-SPECIFIC MANNER*
§¶
,
§,
,
§
Department of Internal Medicine,
Division of Infectious Diseases, § Inflammation Program,
¶ Graduate Programs in Immunology and Molecular Biology, and
** Department of Biochemistry, University of Iowa and
Veterans Affairs Medical Center, Iowa City, Iowa 52242 and

Department of Biochemistry, Kansas
State University, Manhattan, Kansas 66506

-actin was only 45%
as potent and 40% as efficacious as rabbit skeletal muscle
-actin,
whereas its inhibitory profile was similar to the single actin species
from the yeast, Saccharomyces cerevisiae. Use of actin
polymerization-specific reagents indicated that PLD1 binds both
monomeric G-actin, as well as actin filaments. These data are
consistent with a model in which the physical state of the actin
cytoskeleton is a critical determinant of its regulation of PLD activity.
*
This work was supported by National Institutes of Health
Grant RO1 GM62302 and a Veterans Affairs Merit Review grant (to
D. J. K.).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.
To whom correspondence and reprint requests should be
addressed: Dept. of Internal Medicine, University of Iowa, 200 Hawkins Dr., SW 54-I, GH, Iowa City, IA 52242. Tel.: 319-353-6525; Fax: 319-356-4600; E-mail: david-kusner@uiowa.edu.
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