title: The linker region joining the catalytic and the regulatory domains of CnA is essential for binding to NFAT.
abstract: Calcineurin (CN) is an important regulator of developmental processes and in adults controls the immune response through its regulation of nuclear factor of activated T cells (NFAT). The physical interaction between CN and NFATs is an essential step in the activation of NFAT-dependent genes by calcium signals. Using deletional and substitutional analyses, we have identified a 13-amino acid region within CN that is essential for the interaction with NFAT and with two other CN-binding proteins, AKAP79 and Cabin-1. The interaction of CN with these proteins is selectively disrupted by substitution of specific amino acid residues within this region, indicating that NFAT and other CN-interacting proteins bind differentially to CN. This selectivity suggests that the region identified in CN could be a potential molecular target for immunosuppressive and other therapeutic interventions in diseases involving the CN/NFAT pathway.
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares (CNIC), Ronda de Poniente 5, Tres Cantos, Madrid 28760, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodríguez
authors.forename: Sara
authors.initials: S
authors.lastname: Martínez-Martínez
authors.forename: Ma Dolores
authors.initials: MD
authors.lastname: López-Maderuelo
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Ortega-Pérez
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Redondo
mesh_terms: D054758:A Kinase Anchor Proteins; D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry; D019703:Calcineurin / Q000737:chemistry*; D002118:Calcium / Q000378:metabolism; D020134:Catalytic Domain; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000737:chemistry*; D017353:Gene Deletion; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry*; D014162:Transfection
chemical_list: D054758:A Kinase Anchor Proteins; C487775:AKAP5 protein, human; D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D007166:Immunosuppressive Agents; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C468309:cabin-1; D005982:Glutathione Transferase; D019703:Calcineurin; D002118:Calcium