A computationally engineered RAS rheostat reveals RAS-ERK signaling dynamics.

ABSTRACT: Synthetic protein switches controlled with user-defined inputs are powerful tools for studying and controlling dynamic cellular processes. To date, these approaches have relied primarily on intermolecular regulation. Here we report a computationally guided framework for engineering intramolecular regulation of protein function. We utilize this framework to develop chemically inducible activator of RAS (CIAR), a single-component RAS rheostat that directly activates endogenous RAS in response to a small molecule. Using CIAR, we show that direct RAS activation elicits markedly different RAS-ERK signaling dynamics from growth factor stimulation, and that these dynamics differ among cell types. We also found that the clinically approved RAF inhibitor vemurafenib potently primes cells to respond

SUBMITTER: Rose JC 

PROVIDER: S-EPMC5161653 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature