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• W2023542693 abstract "The RAF proteins are cytosolic protein kinases that regulate cell responses to extracellular signals. There are three RAF proteins in cells, ARAF, BRAF and CRAF, and recent studies have shown that the formation of complexes by these different isoforms has an important role in their activation, particularly in response to RAF inhibitors. Here, we investigated the role of ARAF in cancer cell signaling and examined the role of ARAF in mediating paradoxical activation of the MAPK pathway in cells treated with RAF inhibitors. We show that two mutations that occur in ARAF in cancer inactivate the kinase. We also show that ARAF is not functionally redundant with CRAF and cannot substitute for CRAF downstream of RAS. We further show that ARAF binds to and is activated by BRAF and that ARAF also forms complexes with CRAF. Critically, ARAF seems to stabilize BRAF:CRAF complexes in cells treated with RAF inhibitors and thereby regulate cell signaling in a subtle manner to ensure signaling efficiency." @default.
• W2023542693 created "2016-06-24" @default.
• W2023542693 creator A5010711016 @default.
• W2023542693 creator A5050110684 @default.
• W2023542693 date "2012-08-27" @default.
• W2023542693 modified "2023-09-26" @default.
• W2023542693 title "ARAF acts as a scaffold to stabilize BRAF:CRAF heterodimers" @default.
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• W2023542693 doi "https://doi.org/10.1038/onc.2012.330" @default.
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