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 PKCβI 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 PKCβI may be the isozyme responsible for the effects on Ca²⁺ influx. Electroporation of an anti-PKCβI antibody, but not antibodies against PKCα or PKCγ, led to an increase in the rate of Ca²⁺ influx following stimulation. Taken together, these data suggest that PKCβI may be a component of the down-regulation of increases in [Ca²⁺] _i associated with Jurkat T cell activation.

#	Concept	H-Index	Publications	Citations
1	Medicine	2	2	364
2	Biochemistry	1	1	329
3	Cell Biology	1	1	35
4	Cellular Physiology	1	1	35
5	Immunology	1	1	35

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