How to Steer and Control ERK and the ERK Signaling Cascade Exemplified by Looking at Cardiac Insufficiency.

ABSTRACT: Mathematical optimization framework allows the identification of certain nodes within a signaling network. In this work, we analyzed the complex extracellular-signal-regulated kinase 1 and 2 (ERK1/2) cascade in cardiomyocytes using the framework to find efficient adjustment screws for this cascade that is important for cardiomyocyte survival and maladaptive heart muscle growth. We modeled optimal pharmacological intervention points that are beneficial for the heart, but avoid the occurrence of a maladaptive ERK1/2 modification, the autophosphorylation of ERK at threonine 188 (ERK Thr 188 phosphorylation), which causes cardiac hypertrophy. For this purpose, a network of a cardiomyocyte that was fitted to experimental data was equipped with external stimuli that model the pharmacological int

SUBMITTER: Breitenbach T 

PROVIDER: S-EPMC6539830 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature