"Examining RAS pathway rewiring with a chemically inducible activator of RAS". (1st November 2020)

• Record Type: Journal Article
• Authors: Rose, John C.; Dieter, Emily M.; Cunningham-Bryant, Daniel; Maly, Dustin J.
• Is Part Of: Small GTPases. Volume 11:Number 6(2020)
• Page Start: 413
• Page End: 420
• Publication Date: 2020-11-01
• Subjects: Guanosine triphosphatase -- Periodicals; Guanosine triphosphatase; Periodicals; 572.793
• DOI: 10.1080/21541248.2018.1446697
• Languages: English
• ISSNs: 2154-1256

Abstract

ABSTRACT: RAS signaling pathways govern diverse cellular processes, are dynamic, and exhibit marked plasticity. Yet, these features also present a considerable obstacle to their study. Here, we report the use of a recently described RAS rheostat, Chemically Inducible Activator of RAS (CIAR), to study two poorly understood phenomena in RAS biology. First, we show that short-term activation of wild type endogenous RAS can desensitize cells to EGF stimulation. Second, we examine the phenomena of paradoxical activation of RAS/ERK signaling by RAF inhibitors. Specifically, we characterize the effects on RAS/ERK signaling kinetics of four RAF inhibitors, which stabilize distinct ATP-binding site conformations. These results demonstrate the utility of CIAR in conducting quantitative studies of complex features of RAS biology.