ArticleThe EMBO journal1995
Targets of immunophilin-immunosuppressant complexes are distinct highly conserved regions of calcineurin A.
Article in The EMBO journal, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 121 citations in OpenAlex.
- Calcium-dependent serine-threonine phosphatase and autophagy inactivation mediated by Baicalein attenuates prion protein-mediated neuronal cell damage.BMC complementary medicine and therapies · 2025Article
- Calcineurin controls the cytokinesis machinery during thermal stress inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Calcineurin in the heart: New horizons for an old friend.Cellular signalling · 2021Review
- Article
- Calcium-Calmodulin-Calcineurin Signaling: A Globally Conserved Virulence Cascade in Eukaryotic Microbial Pathogens.Cell host & microbe · 2019Review
- Combinatory FK506 and Minocycline Treatment Alleviates Prion-Induced Neurodegenerative Events via Caspase-Mediated MAPK-NRF2 Pathway.International journal of molecular sciences · 2019Article
- X-ray structure of alisporivir in complex with cyclophilin A at 1.5 Å resolution.Acta crystallographica. Section F, Structural biology communications · 2018Article
- FKBP12-Dependent Inhibition of Calcineurin Mediates Immunosuppressive Antifungal Drug Action inmBio · 2017Article
- Early Minocycline and Late FK506 Treatment Improves Survival and Alleviates Neuroinflammation, Neurodegeneration, and Behavioral Deficits in Prion-Infected Hamsters.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017Article
- Calcineurin signaling in the heart: The importance of time and place.Journal of molecular and cellular cardiology · 2017Review
- Calcineurin Targets Involved in Stress Survival and Fungal Virulence.PLoS pathogens · 2016Article
- Calcineurin inhibitors cyclosporine A and tacrolimus induce vascular inflammation and endothelial activation through TLR4 signaling.Scientific reports · 2016Article
- Calcineurin Orchestrates Hyphal Growth, Septation, Drug Resistance and Pathogenesis of Aspergillus fumigatus: Where Do We Go from Here?Pathogens (Basel, Switzerland) · 2015Review
- Calcineurin orchestrates dimorphic transitions, antifungal drug responses and host-pathogen interactions of the pathogenic mucoralean fungus Mucor circinelloides.Molecular microbiology · 2015Article
- Genetic and genomic architecture of the evolution of resistance to antifungal drug combinations.PLoS genetics · 2013Article
- Calcineurin plays key roles in the dimorphic transition and virulence of the human pathogenic zygomycete Mucor circinelloides.PLoS pathogens · 2013Article
- Regulator of calcineurin 1 mediates pathological vascular wall remodeling.The Journal of experimental medicine · 2011Article
- Elucidating the Candida albicans calcineurin signaling cascade controlling stress response and virulence.Fungal genetics and biology : FG & B · 2010Article
- A conserved docking surface on calcineurin mediates interaction with substrates and immunosuppressants.Molecular cell · 2009Article
- Signaling cascades as drug targets in model and pathogenic fungi.Current opinion in investigational drugs (London, England : 2000) · 2008Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The immunosuppressive complexes cyclophilin A-cyclosporin A (CsA) and FKBP12-FK506 inhibit calcineurin, a heterodimeric Ca(2+)-calmodulin-dependent protein phosphatase that regulates signal transduction. We have characterized CsA- or FK506-resistant mutants isolated from a CsA-FK506-sensitive Saccharomyces cerevisiae strain. Three mutations that confer dominant CsA resistance are single amino acid substitutions (T350K, T350R, Y377F) in the calcineurin A catalytic subunit CMP1. One mutation that confers dominant FK506 resistance alters a single residue (W430C) in the calcineurin A catalytic subunit CMP2. In vitro and in vivo, the CsA-resistant calcineurin mutants bind FKBP12-FK506 but have reduced affinity for cyclophilin A-CsA. When introduced into the CMP1 subunit, the FK506 resistance mutation (W388C) blocks binding by FKBP12-FK506, but not by cyclophilin A-CsA. Co-expression of CsA-resistant and FK506-resistant calcineurin A subunits confers resistance to CsA and to FK506 but not to CsA plus FK506. Double mutant calcineurin A subunits (Y377F, W388C CMP1 and Y419F, W430C CMP2) confer resistance to CsA, to FK506 and to CsA plus FK506. These studies identify cyclophilin A-CsA and FKBP12-FK506 binding targets as distinct, highly conserved regions of calcineurin A that overlap the binding domain for the calcineurin B regulatory subunit.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.