| http://purl.uniprot.org/citations/16647110 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16647110 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16647110 | http://www.w3.org/2000/01/rdf-schema#comment | "Phosphoinositide 3-kinases (PI3-Ks) are an important emerging class of drug targets, but the unique roles of PI3-K isoforms remain poorly defined. We describe here an approach to pharmacologically interrogate the PI3-K family. A chemically diverse panel of PI3-K inhibitors was synthesized, and their target selectivity was biochemically enumerated, revealing cryptic homologies across targets and chemotypes. Crystal structures of three inhibitors bound to p110gamma identify a conformationally mobile region that is uniquely exploited by selective compounds. This chemical array was then used to define the PI3-K isoforms required for insulin signaling. We find that p110alpha is the primary insulin-responsive PI3-K in cultured cells, whereas p110beta is dispensable but sets a phenotypic threshold for p110alpha activity. Compounds targeting p110alpha block the acute effects of insulin treatment in vivo, whereas a p110beta inhibitor has no effect. These results illustrate systematic target validation using a matrix of inhibitors that span a protein family."xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.cell.2006.03.035"xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.cell.2006.03.035"xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.uniprot.org/core/author | "Gonzalez B."xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.uniprot.org/core/author | "Gonzalez B."xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.uniprot.org/core/author | "Williams R.L."xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.uniprot.org/core/author | "Williams R.L."xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.uniprot.org/core/author | "Shokat K.M."xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.uniprot.org/core/author | "Shokat K.M."xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.uniprot.org/core/author | "Stokoe D."xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.uniprot.org/core/author | "Stokoe D."xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.uniprot.org/core/author | "Toth B."xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.uniprot.org/core/author | "Toth B."xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.uniprot.org/core/author | "Knight Z.A."xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.uniprot.org/core/author | "Knight Z.A."xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.uniprot.org/core/author | "Weiss W.A."xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.uniprot.org/core/author | "Weiss W.A."xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.uniprot.org/core/author | "Loewith R."xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.uniprot.org/core/author | "Loewith R."xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.uniprot.org/core/author | "Williams O."xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.uniprot.org/core/author | "Williams O."xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.uniprot.org/core/author | "Balla T."xsd:string |
| http://purl.uniprot.org/citations/16647110 | http://purl.uniprot.org/core/author | "Balla T."xsd:string |