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A Role for Protein Kinase CbetaI in the Regulation of Ca2+ Entry in Jurkat T Cells

A Role for Protein Kinase CbetaI in the Regulation of Ca2+ Entry in Jurkat T Cells

D M Haverstick, M Dicus, M S Resnick, J J Sando, L S Gray

J Biol Chem. 1997 Jun 13;272(24):15426-33.

PMID: 9182574

Abstract:

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

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42411914	Protein Kinase CβI isozyme human			Price

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