Isoform-specific sequestration of protein kinase A fine-tunes intracellular signaling during heat stress

Cell Rep. 2024 Jun 25;43(6):114360. doi: 10.1016/j.celrep.2024.114360. Epub 2024 Jun 11.

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.

Keywords: CP: Cell biology; heat stress; protein kinase A; protein sequestration; signaling regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclic AMP-Dependent Protein Kinases* / metabolism
  • Cytoplasmic Granules / metabolism
  • Heat-Shock Response*
  • Isoenzymes / metabolism
  • Protein Binding
  • Protein Isoforms / metabolism
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Saccharomyces cerevisiae* / metabolism
  • Signal Transduction*

Substances

  • Bcy1 protein, S cerevisiae
  • Cyclic AMP-Dependent Protein Kinases
  • Isoenzymes
  • Protein Isoforms
  • Saccharomyces cerevisiae Proteins
  • Tpk3 protein, S cerevisiae