1. The RAS/MAPK Axis Gets Stressed Out
Scott A. Foster, Shiva Malek 
Molecular Cell 
Volume 64, Issue 5, Pages (December 2016)
DOI: /j.molcel
Copyright © 2016 Elsevier Inc. Terms and Conditions

2. Figure 1 Mechanisms of MAPK Pathway Feedback Inhibition
(A) Upon ligand (GF) activation, receptor tyrosine kinases (RTK) undergo autophosphorylation leading to the SOS-dependent conversion of RAS-GDP to RAS-GTP. Active RAS (RAS-GTP) promotes the dimerization and activation or RAF and the subsequent activation of the signaling cascade through MEK and ERK. Upon activation, ERK can translocate into the nucleus, turning on the transcription of pro-growth genes. In addition to its pro-growth role, active ERK also suppresses upstream pathway signaling (ERK-dependent negative feedback) by phosphorylating many components including RAF and SOS.
(B) Rigosterib and other mitotic stress inducers such as Taxol induce the increase in reactive oxygen species (ROS) leading to the activation of JNK signaling. Active JNK can phosphorylate RAF and SOS, resulting in stress-induced suppression of RAS-MAPK signaling.
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2016 Elsevier Inc. Terms and Conditions