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Volume 272, Number 24,
Issue of June 13, 1997
pp. 15426-15433
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
A Role for Protein Kinase C I in the Regulation of
Ca2+ Entry in Jurkat T Cells
(Received for publication, December 30, 1996, and in revised form, March 24, 1997)
Doris M.
Haverstick
,
Michael
Dicus
,
Moira S.
Resnick
¶
,
Julianne J.
Sando
¶
and
Lloyd S.
Gray
From the Departments of Pathology and
¶ Pharmacology, University of Virginia School of Medicine,
Charlottesville, Virginia 22908
T cell activation leading to cytokine production
and cellular proliferation involves a regulated increase and subsequent
decrease in the intracellular concentration of Ca2+
([Ca2+]i). While much is understood about
agonist-induced increases in [Ca2+]i, less is
known about down-regulation of this pathway. Understanding the
mechanism of this down-regulation is critical to the prevention of cell
death that can be the consequence of a sustained elevation in
[Ca2+]i. Protein kinase C (PKC), activated by the
diacylglycerol produced as a consequence of T cell receptor engagement,
has long been presumed to be involved in this down-regulation, although the precise mechanism is not wholly clear. In this report we
demonstrate that activation of PKC by phorbol esters slightly decreases
the rate of Ca2+ efflux from the cytosol of Jurkat T cells
following stimulation through the T cell receptor or stimulation in a
receptor-independent manner by thapsigargin. On the other hand, phorbol
ester treatment dramatically reduces the rate of Ca2+
influx following stimulation. Phorbol ester treatment is without an
effect on Ca2+ influx in a different T cell line, HSB.
Down-regulation of PKC I expression by 18-h phorbol ester treatment
is associated with a loss of the response to acute phorbol ester
treatment in Jurkat cells, suggesting that PKC I may be the isozyme
responsible for the effects on Ca2+ influx. Electroporation
of an anti-PKC I antibody, but not antibodies against PKC or
PKC , led to an increase in the rate of Ca2+ influx
following stimulation. Taken together, these data suggest that PKC I
may be a component of the down-regulation of increases in
[Ca2+]i associated with Jurkat T cell
activation.

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Copyright © 1997 by the American Society for Biochemistry and Molecular Biology.
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