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J Biol Chem, Vol. 273, Issue 29, 18325-18331, July 17, 1998
From the Departments of Neuroscience, § Pharmacology and
Molecular Sciences, and ¶ Psychiatry and Behavioral Sciences,
Johns Hopkins University School of Medicine,
Baltimore, Maryland 21205
Calcineurin is a widely distributed protein
phosphatase regulated by calcium and calmodulin. It mediates the
immunosuppressive actions of drugs such as cyclosporin and FK506, and
has been implicated in a number of calcium-sensitive pathways in the
nervous system, including regulation of neurotransmitter release and
modulation of long-term changes in synaptic plasticity. Calcineurin
associates physiologically with other proteins, including calmodulin,
FKBP12 (FK506-binding protein), the
ryanodine receptor, and the inositol 1,4,5-trisphosphate receptor. We
now report the identification, molecular cloning, and functional
characterization of a novel protein, cain (calcineurin
inhibitor), that interacts with and inhibits calcineurin.
The full-length cain cDNA predicts a 240-kDa protein with no
significant homology to any known protein. Cain associates with
calcineurin both in vitro and in vivo, leading to a non-competitive inhibition of calcineurin activity. The putative calcineurin-binding domain of cain, a 38-amino acid region defined by
mutational analysis, is highly basic. Like calcineurin, cain has a
prominent neuronal expression and a wide tissue distribution. Cain's
expression pattern in the brain closely resembles that of calcineurin,
indicating a physiologic association between the two proteins.
Cain, A Novel Physiologic Protein Inhibitor of Calcineurin
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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