| http://purl.uniprot.org/citations/18794843 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18794843 | http://www.w3.org/2000/01/rdf-schema#comment | "Protein kinases targeted by small-molecule inhibitors develop resistance through mutation of the 'gatekeeper' threonine residue of the active site. Here we show that the gatekeeper mutation in the cellular forms of c-ABL, c-SRC, platelet-derived growth factor receptor-alpha and -beta, and epidermal growth factor receptor activates the kinase and promotes malignant transformation of BaF3 cells. Structural analysis reveals that a network of hydrophobic interactions-the hydrophobic spine-characteristic of the active kinase conformation is stabilized by the gatekeeper substitution. Substitution of glycine for the residues constituting the spine disrupts the hydrophobic connectivity and inactivates the kinase. Furthermore, a small-molecule inhibitor that maximizes complementarity with the dismantled spine (compound 14) inhibits the gatekeeper mutation of BCR-ABL-T315I. These results demonstrate that mutation of the gatekeeper threonine is a common mechanism of activation for tyrosine kinases and provide structural insights to guide the development of next-generation inhibitors."xsd:string |
| http://purl.uniprot.org/citations/18794843 | http://purl.org/dc/terms/identifier | "doi:10.1038/nsmb.1486"xsd:string |
| http://purl.uniprot.org/citations/18794843 | http://purl.uniprot.org/core/author | "Daley G.Q."xsd:string |
| http://purl.uniprot.org/citations/18794843 | http://purl.uniprot.org/core/author | "Kuriyan J."xsd:string |
| http://purl.uniprot.org/citations/18794843 | http://purl.uniprot.org/core/author | "Azam M."xsd:string |
| http://purl.uniprot.org/citations/18794843 | http://purl.uniprot.org/core/author | "Gray N.S."xsd:string |
| http://purl.uniprot.org/citations/18794843 | http://purl.uniprot.org/core/author | "Seeliger M.A."xsd:string |
| http://purl.uniprot.org/citations/18794843 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18794843 | http://purl.uniprot.org/core/name | "Nat Struct Mol Biol"xsd:string |
| http://purl.uniprot.org/citations/18794843 | http://purl.uniprot.org/core/pages | "1109-1118"xsd:string |
| http://purl.uniprot.org/citations/18794843 | http://purl.uniprot.org/core/title | "Activation of tyrosine kinases by mutation of the gatekeeper threonine."xsd:string |
| http://purl.uniprot.org/citations/18794843 | http://purl.uniprot.org/core/volume | "15"xsd:string |
| http://purl.uniprot.org/citations/18794843 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18794843 |
| http://purl.uniprot.org/citations/18794843 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/18794843 |
| http://purl.uniprot.org/uniprot/#_P00523-mappedCitation-18794843 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18794843 |
| http://purl.uniprot.org/uniprot/P00523 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/18794843 |