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PMID: 7593193 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Calcineurin functions in Ca(2+)-activated cell death in mammalian cells.

The Journal of cell biology ·Vol. 131 ·No. 3 ·1995-11-00 ·Pages 735-43

Shibasaki F, McKeon F

Abstract

Calcineurin is a calcium-dependent protein phosphatase that functions in T cell activation. We present evidence that calcineurin functions more generally in calcium-triggered apoptosis in mammalian cells deprived of growth factors. Specifically, expression of epitope-tagged calcineurin A induces rapid cell death upon calcium signaling in the absence of growth factors. We show that this apoptosis does not require new protein synthesis and therefore calcineurin must operate through existing substrates. Co-expression of the Bcl-2 protooncogene efficiently blocks calcineurin-induced cell death. Significantly, we demonstrate that a calcium-independent calcineurin mutant induces apoptosis in the absence of calcium, and that this apoptotic response is a direct consequence of calcineurin's phosphatase activity. These data suggest that calcineurin plays an important role in mediating the upstream events in calcium-activated cell death.

MeSH Terms
Animals Apoptosis/drug effects,physiology Calcineurin Calcium/physiology Calmodulin-Binding Proteins/genetics,physiology Cell Line/cytology,enzymology Cricetinae Gene Expression/physiology Growth Substances/pharmacology Kidney/cytology Mutation Phosphoprotein Phosphatases/genetics,physiology Protein-Tyrosine Kinases/physiology Proto-Oncogene Proteins/physiology Proto-Oncogene Proteins c-bcl-2 Signal Transduction/physiology Substrate Specificity
Chemicals
Calmodulin-Binding Proteins Growth Substances Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 Protein-Tyrosine Kinases Calcineurin Phosphoprotein Phosphatases Calcium
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Shibasaki F
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
McKeon F
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.131.3.735
Published
1995-11-00
Pages
735-43
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2120616
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.131.3.735 PMC Full Text View journal details
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