Mutation-oriented profiling of autoinhibitory kinase conformations predicts RAF inhibitor efficacies.

ABSTRACT: Kinase-targeted therapies have the potential to improve the survival of patients with cancer. However, the cancer-specific spectrum of kinase alterations exhibits distinct functional properties and requires mutation-oriented drug treatments. Besides post-translational modifications and diverse intermolecular interactions of kinases, it is the distinct disease mutation which reshapes full-length kinase conformations, affecting their activity. Oncokinase mutation profiles differ between cancer types, as it was shown for BRAF in melanoma and non-small-cell lung cancers. Here, we present the target-oriented application of a kinase conformation (KinCon) reporter platform for live-cell measurements of autoinhibitory kinase activity states. The bioluminescence-based KinCon biosensor allows the tr

SUBMITTER: Mayrhofer JE 

PROVIDER: S-EPMC7733820 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature