Diacylglycerol mediates the T-cell receptor-driven Ca2+ influx in T cells by a novel mechanism independent of protein kinase C activation
✍ Scribed by Rabindranath Chakrabarti; Sanjeev Kumar
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 174 KB
- Volume
- 78
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
The mechanism of Ca 2ϩ influx in nonexcitable cells is not known yet. According to the capacitative hypothesis, Ca 2ϩ influx is triggered by IP 3 -mediated Ca 2ϩ release from the intracellular Ca 2ϩ stores. Conversely, many workers have reported a lack of association between release and influx. In this work, the role of diacylglycerol (DAG) as the mediator of T-cell receptor (TCR)-driven Ca 2ϩ influx in T cells was investigated. Stimulation of mouse splenic T cells with naturally occurring DAG caused Ca 2ϩ entry in a dose-and time-dependent manner. Such stimulation was blocked by Ni 2ϩ , a divalent cation known to block Ca 2ϩ channels. Inhibition of protein kinase C (PKC) by calphostin C did not inhibit, but slightly enhanced, the DAG-stimulated Ca 2ϩ entry. However, inhibition of DAG metabolism by DAG kinase and lipase inhibitors enhanced the DAG-stimulated Ca 2ϩ entry. DAG lipase and kinase inhibitors also enhanced the Ca 2ϩ entry in T cells stimulated through TCR/CD3 complex with anti-CD3 antibody. Calphostin C did not affect the anti-CD3-stimulated Ca 2ϩ entry. These results showed that TCR-driven Ca 2ϩ influx in T cells is mediated by DAG through a novel mechanism(s) independent of PKC activation.