Abstract IA17: Molecular mechanisms that regulate Raf kinase signaling

Abstract

Abstract Raf kinases are essential for normal Ras pathway signaling, and activating mutations in components of this pathway are associated with a variety of human cancers as well as a group of related developmental disorders known collectively as the RASopathies. Of the core pathway components, the mechanisms that modulate the Raf family kinases are by far the most complex, involving changes in subcellular localization, protein interactions, and phosphorylation/dephosphorylation events. In addition, like numerous other protein kinases, the Raf kinases can form dimers. Functional studies investigating the importance of Raf dimerization have revealed that Raf dimer formation is required for normal Ras-dependent Raf activation and for the biologic activity of many disease-associated Raf mutants. At the meeting, I will present recent work examining the regulatory differences among Raf family members and will discuss how these differences contribute to Raf-mediated disease signaling. I will also present studies investigating the effect that various therapeutic agents have on Raf regulatory interactions and will describe new approaches to disrupt Ras-Raf-MEK-ERK pathway signaling. Citation Format: Deborah Morrison. Molecular mechanisms that regulate Raf kinase signaling [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr IA17.