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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
1996-1-24
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pubmed:abstractText |
The immunosuppressant drug FK506 binds to the immunophilin protein FKBP12 and inhibits its prolyl isomerase activity. Immunosuppressive actions, however, are mediated via an FK506-FKBP12 inhibition of the Ca(2+)-activated phosphatase calcineurin. Physiologic cellular roles for FKBP12 have remained unclear. FKBP12 is physically associated with the RyR and IP3R Ca2+ channels in the absence of FK506, with added FK506 disrupting these complexes. Dissociation of FKBP12 results in alteration of channel Ca2+ conductance in both cases. We now report that calcineurin is physiologically associated with the IP3R-FKBP12 and RyR-FKBP12 receptor complexes and that this interaction can be disrupted by FK506 or rapamycin. Calcineurin anchored to the IP3R via FKBP12 regulates the phosphorylation status of the receptor, resulting in a dynamic Ca(2+)-sensitive regulation of IP3-mediated Ca2+ flux.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antifungal Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Calcineurin,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Calmodulin-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Immunosuppressive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate...,
http://linkedlifedata.com/resource/pubmed/chemical/Muscle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Polyenes,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Ryanodine Receptor Calcium Release...,
http://linkedlifedata.com/resource/pubmed/chemical/Sirolimus,
http://linkedlifedata.com/resource/pubmed/chemical/Tacrolimus,
http://linkedlifedata.com/resource/pubmed/chemical/Tacrolimus Binding Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0092-8674
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
3
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pubmed:volume |
83
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
463-72
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:8521476-Animals,
pubmed-meshheading:8521476-Antifungal Agents,
pubmed-meshheading:8521476-Calcineurin,
pubmed-meshheading:8521476-Calcium,
pubmed-meshheading:8521476-Calcium Channels,
pubmed-meshheading:8521476-Calmodulin-Binding Proteins,
pubmed-meshheading:8521476-Carrier Proteins,
pubmed-meshheading:8521476-Cells, Cultured,
pubmed-meshheading:8521476-Cerebellum,
pubmed-meshheading:8521476-DNA-Binding Proteins,
pubmed-meshheading:8521476-Heat-Shock Proteins,
pubmed-meshheading:8521476-Immunosuppressive Agents,
pubmed-meshheading:8521476-Inositol 1,4,5-Trisphosphate,
pubmed-meshheading:8521476-Inositol 1,4,5-Trisphosphate Receptors,
pubmed-meshheading:8521476-Muscle Proteins,
pubmed-meshheading:8521476-Phosphoprotein Phosphatases,
pubmed-meshheading:8521476-Phosphorylation,
pubmed-meshheading:8521476-Polyenes,
pubmed-meshheading:8521476-Precipitin Tests,
pubmed-meshheading:8521476-Rats,
pubmed-meshheading:8521476-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:8521476-Ryanodine Receptor Calcium Release Channel,
pubmed-meshheading:8521476-Sirolimus,
pubmed-meshheading:8521476-Tacrolimus,
pubmed-meshheading:8521476-Tacrolimus Binding Proteins
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pubmed:year |
1995
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pubmed:articleTitle |
Calcineurin associated with the inositol 1,4,5-trisphosphate receptor-FKBP12 complex modulates Ca2+ flux.
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pubmed:affiliation |
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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