| http://purl.uniprot.org/citations/34171264 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34171264 | http://www.w3.org/2000/01/rdf-schema#comment | "Activating mutations in HER2 (ERBB2) drive the growth of a subset of breast and other cancers and tend to co-occur with HER3 (ERBB3) missense mutations. The HER2 tyrosine kinase inhibitor neratinib has shown clinical activity against HER2-mutant tumors. To characterize the role of HER3 mutations in HER2-mutant tumors, we integrate computational structural modeling with biochemical and cell biological analyses. Computational modeling predicts that the frequent HER3E928G kinase domain mutation enhances the affinity of HER2/HER3 and reduces binding of HER2 to its inhibitor neratinib. Co-expression of mutant HER2/HER3 enhances HER2/HER3 co-immunoprecipitation and ligand-independent activation of HER2/HER3 and PI3K/AKT, resulting in enhanced growth, invasiveness, and resistance to HER2-targeted therapies, which can be reversed by combined treatment with PI3Kα inhibitors. Our results provide a mechanistic rationale for the evolutionary selection of co-occurring HER2/HER3 mutations and the recent clinical observations that HER3 mutations are associated with a poor response to neratinib in HER2-mutant cancers."xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ccell.2021.06.001"xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/author | "He J."xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/author | "Ye D."xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/author | "Chatterjee S."xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/author | "Lin C.C."xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/author | "Lee K.M."xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/author | "Akamatsu H."xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/author | "Arteaga C.L."xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/author | "Sheehan J.H."xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/author | "Marin A."xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/author | "Meiler J."xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/author | "Brown B.P."xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/author | "Lalani A.S."xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/author | "Koch J.P."xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/author | "Hanker A.B."xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/author | "Servetto A."xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/author | "Sudhan D.R."xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/author | "Brewer M.R."xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/author | "Jayanthan H.S."xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/name | "Cancer Cell"xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/pages | "1099-1114.e8"xsd:string |
| http://purl.uniprot.org/citations/34171264 | http://purl.uniprot.org/core/title | "Co-occurring gain-of-function mutations in HER2 and HER3 modulate HER2/HER3 activation, oncogenesis, and HER2 inhibitor sensitivity."xsd:string |