title: RCAN 1 and 3 proteins regulate thymic positive selection.
abstract: Cooperation between calcineurin (CN)-NFATc and RAF-MEK-ERK signaling pathways is essential in thymocyte positive selection. It is known that the Regulators of Calcineurin (RCAN) proteins can act either facilitating or suppressing CN-dependent signaling events. Here, we show that RCAN genes are expressed in lymphoid tissues, and address the role of RCAN proteins in T cell development. Overexpression of human RCAN3 and RCAN1 can modulate T cell development by increasing positive selection-related surface markers, as well as the "Erk(hi) competence state" in double positive thymocytes, a characteristic molecular signature of positive selection, without affecting CN activity. We also found that RCAN1/3 interact with RAF kinases and CN in a non-exclusive manner. Our data suggests that the balance of RCAN interactions with CN and/or RAF kinases may influence T cell positive selection.
authors.affiliation: Human Molecular Genetics Laboratory, Cell Signaling Unit, Bellvitge Biomedical Research Institute - IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Serrano-Candelas
authors.affiliation: Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, México DF 04510, Mexico.
authors.forename: Germán
authors.initials: G
authors.lastname: Alemán-Muench
authors.affiliation: Human Molecular Genetics Laboratory, Cell Signaling Unit, Bellvitge Biomedical Research Institute - IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain.
authors.forename: Sònia
authors.initials: S
authors.lastname: Solé-Sánchez
authors.affiliation: Human Molecular Genetics Laboratory, Cell Signaling Unit, Bellvitge Biomedical Research Institute - IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Aubareda
authors.affiliation: Human Molecular Genetics Laboratory, Cell Signaling Unit, Bellvitge Biomedical Research Institute - IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Martínez-Høyer
authors.affiliation: LEITAT Technological Center, Biomed Divison, Parc Científic de Barcelona, Barcelona 08028, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Adán
authors.affiliation: Human Molecular Genetics Laboratory, Cell Signaling Unit, Bellvitge Biomedical Research Institute - IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Aranguren-Ibáñez
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3168, Australia.
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Pritchard
authors.affiliation: Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, México DF 04510, Mexico. Electronic address: soldevi@unam.mx.
authors.forename: Gloria
authors.initials: G
authors.lastname: Soldevila
authors.affiliation: Human Molecular Genetics Laboratory, Cell Signaling Unit, Bellvitge Biomedical Research Institute - IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain. Electronic address: mpr@idibell.cat.
authors.forename: Mercè
authors.initials: M
authors.lastname: Pérez-Riba
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000276:immunology / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000276:immunology / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D013950:Thymus Gland / Q000196:embryology / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; C511512:DSCR1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C000599749:RCAN3 protein, mouse
keywords: Calcineurin; NFATc; RAF kinase; RCAN1; RCAN3; Thymocyte positive selection