Systems Level Analysis of Time and Stimuli Specific Signaling Through PKA

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2024 Mar 6

PMID 38446618

Authors

Michael Plank

Nicole Carmiol

Bassam Mitri

Austin A Lipinski

Paul R Langlais

Andrew P Capaldi

Affiliations

Soon will be listed here.

Abstract

It is well known that eukaryotic cells create gradients of cAMP across space and time to regulate the cAMP dependent protein kinase (PKA) and, in turn, growth and metabolism. However, it is unclear how PKA responds to different concentrations of cAMP. Here, to address this question, we examine PKA signaling in in different conditions, timepoints, and concentrations of the chemical inhibitor 1-NM-PP1, using phosphoproteomics. These experiments show that there are numerous proteins that are only phosphorylated when cAMP and PKA activity are at/near their maximum level, while other proteins are phosphorylated even when cAMP levels and PKA activity are low. The data also show that PKA drives cells into distinct growth states by acting on proteins with different thresholds for phosphorylation in different conditions. Analysis of the sequences surrounding the 118 PKA-dependent phosphosites suggests that the phosphorylation thresholds are set, at least in part, by the affinity of PKA for each site.

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