Membrane localization of acetylated CNK1 mediates a positive feedback on RAF/ERK signaling.

ABSTRACT: Spatiotemporal control is a common mechanism that modulates activity and function of signal transducers in the signaling network. We identified acetylation of CNK1 (connector enhancer of kinase suppressor of Ras-1) as a late step in the activation of CNK1 signaling, accompanied with prolonged stimulation of extracellular signal-regulated kinase (ERK). We identified the acetyltransferase CREB (cyclic adenosine 3',5'-monophosphate response element-binding protein)-binding protein and the deacetylase SIRT2 (sirtuin type 2) as novel binding partners of CNK1, modulating the acetylation state of CNK1. Acetylation of CNK1 at position Lys⁴¹⁴ located in the pleckstrin homology domain drives membrane localization of CNK1 in growth factor-stimulated cells. Inhibition of ERK signaling aboli

SUBMITTER: Fischer A 

PROVIDER: S-EPMC5553820 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature