| http://purl.uniprot.org/citations/26173259 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26173259 | http://www.w3.org/2000/01/rdf-schema#comment | "Class IB phosphoinositide 3-kinases γ (PI3Kγ) are second-messenger-generating enzymes downstream of signalling cascades triggered by G-protein-coupled receptors (GPCRs). PI3Kγ variants have one catalytic p110γ subunit that can form two different heterodimers by binding to one of a pair of non-catalytic subunits, p87 or p101. Growing experimental data argue for a different regulation of p87-p110γ and p101-p110γ allowing integration into distinct signalling pathways. Pharmacological tools enabling distinct modulation of the two variants are missing. The ability of an anti-p110γ monoclonal antibody [mAb(A)p110γ] to block PI3Kγ enzymatic activity attracted us to characterize this tool in detail using purified proteins. In order to get insight into the antibody-p110γ interface, hydrogen-deuterium exchange coupled to MS (HDX-MS) measurements were performed demonstrating binding of the monoclonal antibody to the C2 domain in p110γ, which was accompanied by conformational changes in the helical domain harbouring the Gβγ-binding site. We then studied the modulation of phospholipid vesicles association of PI3Kγ by the antibody. p87-p110γ showed a significantly reduced Gβγ-mediated phospholipid recruitment as compared with p101-p110γ. Concomitantly, in the presence of mAb(A)p110γ, Gβγ did not bind to p87-p110γ. These data correlated with the ability of the antibody to block Gβγ-stimulated lipid kinase activity of p87-p110γ 30-fold more potently than p101-p110γ. Our data argue for differential regulatory functions of the non-catalytic subunits and a specific Gβγ-dependent regulation of p101 in PI3Kγ activation. In this scenario, we consider the antibody as a valuable tool to dissect the distinct roles of the two PI3Kγ variants downstream of GPCRs."xsd:string |
| http://purl.uniprot.org/citations/26173259 | http://purl.org/dc/terms/identifier | "doi:10.1042/bj20150099"xsd:string |
| http://purl.uniprot.org/citations/26173259 | http://purl.uniprot.org/core/author | "Hirsch E."xsd:string |
| http://purl.uniprot.org/citations/26173259 | http://purl.uniprot.org/core/author | "Williams R.L."xsd:string |
| http://purl.uniprot.org/citations/26173259 | http://purl.uniprot.org/core/author | "Krause E."xsd:string |
| http://purl.uniprot.org/citations/26173259 | http://purl.uniprot.org/core/author | "Brenowitz M."xsd:string |
| http://purl.uniprot.org/citations/26173259 | http://purl.uniprot.org/core/author | "Czupalla C."xsd:string |
| http://purl.uniprot.org/citations/26173259 | http://purl.uniprot.org/core/author | "Wetzker R."xsd:string |
| http://purl.uniprot.org/citations/26173259 | http://purl.uniprot.org/core/author | "Harteneck C."xsd:string |
| http://purl.uniprot.org/citations/26173259 | http://purl.uniprot.org/core/author | "Nurnberg B."xsd:string |
| http://purl.uniprot.org/citations/26173259 | http://purl.uniprot.org/core/author | "Shymanets A."xsd:string |
| http://purl.uniprot.org/citations/26173259 | http://purl.uniprot.org/core/author | "Ghigo A."xsd:string |
| http://purl.uniprot.org/citations/26173259 | http://purl.uniprot.org/core/author | "Vadas O."xsd:string |
| http://purl.uniprot.org/citations/26173259 | http://purl.uniprot.org/core/author | "LoPiccolo J."xsd:string |
| http://purl.uniprot.org/citations/26173259 | http://purl.uniprot.org/core/author | "Prajwal"xsd:string |
| http://purl.uniprot.org/citations/26173259 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26173259 | http://purl.uniprot.org/core/name | "Biochem J"xsd:string |
| http://purl.uniprot.org/citations/26173259 | http://purl.uniprot.org/core/pages | "59-69"xsd:string |
| http://purl.uniprot.org/citations/26173259 | http://purl.uniprot.org/core/title | "Different inhibition of Gbetagamma-stimulated class IB phosphoinositide 3-kinase (PI3K) variants by a monoclonal antibody. Specific function of p101 as a Gbetagamma-dependent regulator of PI3Kgamma enzymatic activity."xsd:string |
| http://purl.uniprot.org/citations/26173259 | http://purl.uniprot.org/core/volume | "469"xsd:string |
| http://purl.uniprot.org/citations/26173259 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26173259 |
| http://purl.uniprot.org/citations/26173259 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/26173259 |
| http://purl.uniprot.org/uniprot/#_A8K9G9-mappedCitation-26173259 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26173259 |
| http://purl.uniprot.org/uniprot/#_Q24M88-mappedCitation-26173259 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26173259 |