Creamer, Declan R, Beynon, Robert J 
ORCID: 0000-0003-0857-495X, Hubbard, Simon J, Ashe, Mark P and Grant, Chris M
(2024)
Isoform-specific sequestration of protein kinase A fine-tunes intracellular signaling during heat stress.
Cell reports, 43 (6).
p. 114360.
ISSN 2211-1247, 2211-1247
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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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Cytoplasmic Granules, Saccharomyces cerevisiae, Isoenzymes, Cyclic AMP-Dependent Protein Kinases, Saccharomyces cerevisiae Proteins, Protein Isoforms, Signal Transduction, Protein Binding, Heat-Shock Response |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 25 Jun 2024 10:06 |
| Last Modified: | 08 Dec 2024 03:09 |
| DOI: | 10.1016/j.celrep.2024.114360 |
| Related Websites: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3182368 |
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