title: Protein Kinase C δ: a Gatekeeper of Immune Homeostasis.
abstract: Human autoimmune disorders present in various forms and are associated with a life-long burden of high morbidity and mortality. Many different circumstances lead to the loss of immune tolerance and often the origin is suspected to be multifactorial. Recently, patients with autosomal recessive mutations in PRKCD encoding protein kinase c delta (PKCδ) have been identified, representing a monogenic prototype for one of the most prominent forms of humoral systemic autoimmune diseases, systemic lupus erythematosus (SLE). PKCδ is a signaling kinase with multiple downstream target proteins and with functions in various signaling pathways. Interestingly, mouse models have indicated a special role of the ubiquitously expressed protein in the control of B-cell tolerance revealed by the severe autoimmunity in Prkcd (-/-) knockout mice as the major phenotype. As such, the study of PKCδ deficiency in humans has tremendous potential in enhancing our knowledge on the mechanisms of B-cell tolerance.
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT 25.3, Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Salzer
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT 25.3, Vienna, Austria.
authors.forename: Elisangela
authors.initials: E
authors.lastname: Santos-Valente
authors.affiliation: Center for Chronic Immunodeficiency, University Medical Center Freiburg and University of Freiburg, Freiburg, Germany.
authors.forename: Bärbel
authors.initials: B
authors.lastname: Keller
authors.affiliation: Center for Chronic Immunodeficiency, University Medical Center Freiburg and University of Freiburg, Freiburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Warnatz
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT 25.3, Vienna, Austria. kboztug@cemm.oeaw.ac.at.|Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Lazarettgasse 14 AKH BT 25.3, Vienna, Austria. kboztug@cemm.oeaw.ac.at.|Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases and CeRUD Vienna Center for Rare and Undiagnosed Diseases, Vienna, Austria. kboztug@cemm.oeaw.ac.at.
authors.forename: Kaan
authors.identifier: 0000-0001-8387-9185
authors.initials: K
authors.lastname: Boztug
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000235:genetics; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006706:Homeostasis; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D007109:Immunity; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D008214:Lymphocytes; D018345:Mice, Knockout; D009154:Mutation; D010641:Phenotype; D010766:Phosphorylation; D051745:Protein Kinase C-delta / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
chemical_list: D051745:Protein Kinase C-delta
keywords: PRKCD; autoimmunity; immunodeficiency; systemic lupus erythematosus