| http://purl.uniprot.org/citations/25133428 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25133428 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25133428 | http://www.w3.org/2000/01/rdf-schema#comment | "Recently, patient mutations that activate PI3K signaling have been linked to a primary antibody deficiency. Here, we used whole-exome sequencing and characterized the molecular defects in 4 patients from 3 unrelated families diagnosed with hypogammaglobulinemia and recurrent infections. We identified 2 different heterozygous splice site mutations that affect the same splice site in PIK3R1, which encodes the p85α subunit of PI3K. The resulting deletion of exon 10 produced a shortened p85α protein that lacks part of the PI3K p110-binding domain. The hypothetical loss of p85α-mediated inhibition of p110 activity was supported by elevated phosphorylation of the known downstream signaling kinase AKT in patient T cell blasts. Analysis of patient blood revealed that naive T and memory B cell counts were low, and T cell blasts displayed enhanced activation-induced cell death, which was corrected by addition of the PI3Kδ inhibitor IC87114. Furthermore, B lymphocytes proliferated weakly in response to activation via the B cell receptor and TLR9, indicating a B cell defect. The phenotype exhibited by patients carrying the PIK3R1 splice site mutation is similar to that of patients carrying gain-of-function mutations in PIK3CD. Our results suggest that PI3K activity is tightly regulated in T and B lymphocytes and that various defects in the PI3K-triggered pathway can cause primary immunodeficiencies."xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci75746"xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci75746"xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.uniprot.org/core/author | "Fischer A."xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.uniprot.org/core/author | "Fischer A."xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.uniprot.org/core/author | "Bole-Feysot C."xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.uniprot.org/core/author | "Bole-Feysot C."xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.uniprot.org/core/author | "Nitschke P."xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.uniprot.org/core/author | "Nitschke P."xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.uniprot.org/core/author | "Durandy A."xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.uniprot.org/core/author | "Durandy A."xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.uniprot.org/core/author | "Cavazzana M."xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.uniprot.org/core/author | "Cavazzana M."xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.uniprot.org/core/author | "Deau M.C."xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.uniprot.org/core/author | "Deau M.C."xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.uniprot.org/core/author | "Heurtier L."xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.uniprot.org/core/author | "Heurtier L."xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.uniprot.org/core/author | "Kracker S."xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.uniprot.org/core/author | "Kracker S."xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.uniprot.org/core/author | "Picard C."xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.uniprot.org/core/author | "Picard C."xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.uniprot.org/core/author | "Frange P."xsd:string |
| http://purl.uniprot.org/citations/25133428 | http://purl.uniprot.org/core/author | "Frange P."xsd:string |