ERK activation is only one role of PKC in TCR-independent cytotoxic T cell granule exocytosis.

Biochemical and Biophysical Research Communications
Arun T Pores-FernandoAdam Zweifach

Abstract

Cytotoxic T cells (CTLs) kill target cells by releasing lytic agents via regulated exocytosis. Three signals are known to be required for exocytosis: an increase in intracellular Ca(2+), activation of protein kinase C (PKC) and activation of extracellular signal regulated signal kinase (ERK). ERK activation required for exocytosis depends on activity of PKC. The simplest possibility is that the sole effect of PKC required for exocytosis is ERK activation. Testing this requires dissociating ERK and PKC activation. We did this using TCR-independent stimulation of TALL-104 human leukemic CTLs. When cells are stimulated with thapsigargin and PMA, agents that increase intracellular Ca(2+) and activate PKC, respectively, PKC-dependent ERK activation is required for lytic granule exocytosis. Expressing a constitutively active mutant MAP kinase kinase activates ERK independent of PKC. However, activating ERK without PKC does not support lytic granule exocytosis, indicating that there are multiple effects of PKC required for granule exocytosis.

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Citations

Jul 14, 2009·The Journal of Biological Chemistry·Arun T Pores-FernandoAdam Zweifach
Jul 2, 2011·Molecular Endocrinology·Jen-Chieh ChuangJeffrey M Zigman
Sep 17, 2009·Immunological Reviews·Arun T Pores-Fernando, Adam Zweifach
Mar 2, 2017·Cell Biology and Toxicology·Ting CaoPeng Zhang

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