title: Dysfunctional cytokine receptor signaling in severe combined immunodeficiency.
abstract: I have reviewed the data demonstrating that XSCID results from mutations in gamma c and that an autosomal recessive form of SCID results from mutations in Jak3, a kinase that interacts with gamma c and is responsible for transducing gamma c-dependent signals. These findings underscore the dysfunctional cytokine receptor signaling that occurs in at least two forms of SCID. Features of the biology of Jak-STAT pathways have been discussed, as have the potential roles of overactive Jak-STAT pathways in cellular transformation. Implicit in these findings are the exciting possibilities of gene therapy for XSCID and Jak3-deficient SCID, as well as the possibility that new immunosuppressive drugs might be based on the ability to disrupt Jak-STAT pathways.
authors.affiliation: Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1674, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Leonard
mesh_terms: D000818:Animals; D006801:Humans; D017354:Point Mutation; D018121:Receptors, Cytokine / Q000235:genetics* / Q000502:physiology; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D015398:Signal Transduction
chemical_list: D018121:Receptors, Cytokine