PubMed:30994353 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/30994353","sourcedb":"PubMed","sourceid":"30994353","source_url":"https://www.ncbi.nlm.nih.gov/pubmed/30994353","text":"Quantitative Interrogation of the Human Kinome Perturbed by Two BRAF Inhibitors.\nOncogenic BRAF mutations contribute to the development of a number of cancers, and small-molecule BRAF inhibitors have been approved by the Food and Drug Administration (FDA) for anticancer therapy. In this study, we employed two targeted quantitative proteomics approaches for monitoring separately the alterations in protein expression and ATP binding affinities of kinases in cultured human melanoma cells elicited by two FDA-approved small-molecule BRAF inhibitors, dabrafenib and vemurafenib. Our results showed that treatment with the two inhibitors led to markedly different reprograming of the human kinome. Furthermore, we confirmed that vemurafenib could compromise the ATP binding capacity of MAP2K5 in vitro and inhibit its kinase activity in cells. Together, our targeted quantitative proteomic methods revealed profound changes in expression levels of kinase proteins in cultured melanoma cells upon treatment with clinically used BRAF inhibitors and led to the discovery of novel putative target kinases for these 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