These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Protein kinase C activation inhibits TCR-mediated calcium influx but not inositol trisphosphate production in HPB-ALL T cells.
    Author: Shivnan E, Alexander DR.
    Journal: J Immunol; 1995 Feb 01; 154(3):1146-56. PubMed ID: 7822790.
    Abstract:
    The regulation by protein kinase C (PKC) of TCR-mediated changes in phosphoinositide metabolism and intracellular calcium ([Ca2+]i) was investigated in HPB-ALL T cells. Low concentrations (< 1 microgram/ml) of the anti-CD3 OKT3 mAb triggered large calcium signals but not detectable increase in D-myo-inositol 1,4,5-trisophate (IP3) production. CD3-CD4 coligation amplified the calcium signal twofold, compared with CD3 cross-linking alone, but this protocol also did not stimulate IP3 production. At higher OKT3 concentrations (> 2.5 micrograms/ml), IP3 production was detected but was not inhibited by activating PKC with phorbol ester. In contrast, PKC activation caused a marked inhibition (53 to 64%) of the CD3- or CD3-CD4-triggered calcium signals, but had only a small inhibitory effect (20 to 30%) on the release of intracellular Ca2+. PKC activation also inhibited by 47% calcium signals triggered by thapsigargin, an inhibition that was completely reversed by addition of the specific PKC inhibitor RO 31-8220 (1 microM). Addition of 1 microM RO 31-8220 caused a twofold stimulation of CD3-induced calcium signals. This effect was not mediated at the level of Ca2+ influx, because RO 31-8220 did not significantly increase thapsigargin-triggered calcium signals. However, RO 31-8220 did slightly increase the CD3-induced release of intracellular Ca2+, suggesting that amplification of Ca2+ influx may be secondary to increased release of Ca2+ from intracellular stores. Our results indicate that PKC regulates TCR-mediated changes in [Ca2+]i in HPB-ALL T cells by two distinct mechanisms. First, PKC activation causes a marked inhibition of Ca2+ influx by a mechanism independent of changes in IP3 production, possibly involving inhibition of ion channels. Second, PKC activity causes a small inhibition of intracellular Ca2+ release, most likely by promoting Ca2+ sequestration.
    [Abstract] [Full Text] [Related] [New Search]