Isoform-specific sequestration of protein kinase A fine-tunes intracellular signaling during heat stress.
Cell Rep
; 43(6): 114360, 2024 Jun 25.
Article
de En
| MEDLINE
| ID: mdl-38865242
ABSTRACT
Protein kinase A (PKA) is a conserved kinase crucial for fundamental biological processes linked to growth, development, and metabolism. The PKA catalytic subunit is expressed as multiple isoforms in diverse eukaryotes; however, their contribution to ensuring signaling specificity in response to environmental cues remains poorly defined. Catalytic subunit activity is classically moderated via interaction with an inhibitory regulatory subunit. Here, a quantitative mass spectrometry approach is used to examine heat-stress-induced changes in the binding of yeast Tpk1-3 catalytic subunits to the Bcy1 regulatory subunit. We show that Tpk3 is not regulated by Bcy1 binding but, instead, is deactivated upon heat stress via reversible sequestration into cytoplasmic granules. These "Tpk3 granules" are enriched for multiple PKA substrates involved in various metabolic processes, with the Hsp42 sequestrase required for their formation. Hence, regulated sequestration of Tpk3 provides a mechanism to control isoform-specific kinase signaling activity during stress conditions.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Saccharomyces cerevisiae
/
Transduction du signal
/
Cyclic AMP-Dependent Protein Kinases
/
Réaction de choc thermique
/
Protéines de Saccharomyces cerevisiae
Langue:
En
Journal:
Cell Rep
Année:
2024
Type de document:
Article
Pays d'affiliation:
Royaume-Uni