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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.
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]
Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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DbLabel: Engineering Source
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PubType: Academic Journal
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  Data: Cross-talk with Ca<superscript>2+</superscript> Influx Does Not Underlie the Role of Extracellular Signal-regulated Kinases in Cytotoxic T Lymphocyte Lytic Granule Exocytosis.
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  Data: <searchLink fieldCode="AR" term="%22Fierro%2C+Allan+F%2E%22">Fierro, Allan F.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Wurth%2C+Georjeana+A%2E%22">Wurth, Georjeana A.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Zweifach%2C+Adam%22">Zweifach, Adam</searchLink><relatesTo>1</relatesTo><i> adam.zweifach@UCHSC.edu</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. 6/11/2004, Vol. 279 Issue 24, p25646-25652. 7p. 6 Black and White Photographs, 12 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Lymphocytes%22">Lymphocytes</searchLink><br /><searchLink fieldCode="DE" term="%22T+cells%22">T cells</searchLink><br /><searchLink fieldCode="DE" term="%22Immunoglobulins%22">Immunoglobulins</searchLink><br /><searchLink fieldCode="DE" term="%22Leukocytes%22">Leukocytes</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+kinase+C%22">Protein kinase C</searchLink><br /><searchLink fieldCode="DE" term="%22Molecular+cloning%22">Molecular cloning</searchLink><br /><searchLink fieldCode="DE" term="%22Monoclonal+antibodies%22">Monoclonal antibodies</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: 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]
– Name: AbstractSuppliedCopyright
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  Group: Ab
  Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1074/jbc.M400296200
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      – Code: eng
        Text: English
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        StartPage: 25646
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      – SubjectFull: Lymphocytes
        Type: general
      – SubjectFull: T cells
        Type: general
      – SubjectFull: Immunoglobulins
        Type: general
      – SubjectFull: Leukocytes
        Type: general
      – SubjectFull: Protein kinase C
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      – SubjectFull: Molecular cloning
        Type: general
      – SubjectFull: Monoclonal antibodies
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      – TitleFull: 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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            NameFull: Wurth, Georjeana A.
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              M: 06
              Text: 6/11/2004
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              Y: 2004
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