Cross-talk with Ca2+ Influx Does Not Underlie the Role of Extracellular Signal-regulated Kinases in Cytotoxic T Lymphocyte Lytic Granule Exocytosis.
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| Title: | Cross-talk with Ca2+ Influx Does Not Underlie the Role of Extracellular Signal-regulated Kinases in Cytotoxic T Lymphocyte Lytic Granule Exocytosis. |
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| Authors: | Fierro, Allan F.1, Wurth, Georjeana A.1, Zweifach, Adam1 adam.zweifach@UCHSC.edu |
| Source: | Journal of Biological Chemistry. 6/11/2004, Vol. 279 Issue 24, p25646-25652. 7p. 6 Black and White Photographs, 12 Graphs. |
| Subjects: | Lymphocytes, T cells, Immunoglobulins, Leukocytes, Protein kinase C, Molecular cloning, Monoclonal antibodies |
| Abstract: | One important mechanism cytotoxic T lymphocytes use to kill target cells is exocytosis of lytic granules that contain cytotoxic agents such as perforin and granzyme. Ca2+ influx and activation of protein kinase C have been known for many years to be key signals for granule exocytosis. Recent work has suggested that activation of extracellular signal-regulated kinases (ERK), members of the mitogen-activated protein kinase (MAP kinase) family, may be a third required signal. We surmised that the involvement of ERK in lytic granule exocytosis could be mediated through cross-talk with Ca2+ influx, rather than constituting an independent signal. We tested this idea using TALL-104 human leukemic CTLs as a model system and discovered the following. 1) ERK inhibition caused a modest decrease in the amplitude of increases in intracellular Ca2+ concentration, but this effect cannot account for the profound inhibition of granule exocytosis. 2) Ca2+ influx can activate ERK in TALL-104 cells, but this effect does not contribute to ERK activation stimulated by solid phase anti-CD3 monoclonal antibodies. We conclude that cross-talk between ERK signaiing and Ca2+ does not mediate the role of ERK in CTL lytic granule exocytosis. [ABSTRACT FROM AUTHOR] |
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| Database: | Engineering Source |
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