Yeast Protein Kinase A Isoforms: A Means of Encoding Specificity in the Response to Diverse Stress Conditions?

Abstract

Eukaryotic cells have developed a complex circuitry of signalling molecules which monitor changes in their intra- and extracellular environments. One of the most widely studied signalling pathways is the highly conserved cyclic AMP (cAMP)/protein kinase A (PKA) pathway, which is a major glucose sensing circuit in the yeast Saccharomyces cerevisiae. PKA activity regulates diverse targets in yeast, positively activating the processes that are associated with rapid cell growth (e.g., fermentative metabolism, ribosome biogenesis and cell division) and negatively regulating the processes that are associated with slow growth, such as respiratory growth, carbohydrate storage and entry into stationary phase. As in higher eukaryotes, yeast has evolved complexity at the level of the PKA catalytic subunit, and Saccharomyces cerevisiae expresses three isoforms, denoted Tpk1-3. Despite evidence for isoform differences in multiple biological processes, the molecular basis of PKA signalling specificity remains poorly defined, and many studies continue to assume redundancy with regards to PKA-mediated regulation. PKA has canonically been shown to play a key role in fine-tuning the cellular response to diverse stressors; however, recent studies have now begun to interrogate the requirement for individual PKA catalytic isoforms in coordinating distinct steps in stress response pathways. In this review, we discuss the known non-redundant functions of the Tpk catalytic subunits and the evolving picture of how these isoforms establish specificity in the response to different stress conditions.

AlacatDesigner─Computational Design of Peptide Concatamers for Protein Quantitation

“…As a case study, we tested the utility of the software to design standards for the widely studied cAMP-dependent protein kinase (PKA) from Saccharomyces cerevisiae . This kinase is a tetrameric complex, comprising two regulatory subunits (encoded by BCY1 ) and two catalytic subunits (encoded by either TPK1 , TPK2 , or TPK3 ) . To generate an ALACAT representative of these four subunits, UniProt accession numbers P05986, P06244, P06245, and P07278 were presented to the AlacatDesigner.…”

“…This kinase is a tetrameric complex, comprising two regulatory subunits (encoded by BCY1 ) and two catalytic subunits (encoded by either TPK1 , TPK2 , or TPK3 ). 36 To generate an ALACAT representative of these four subunits, UniProt accession numbers P05986, P06244, P06245, and P07278 were presented to the AlacatDesigner. As the user can specify peptides of their choosing, we also included two peptides per subunit that had been detected in a recent chemostat quantification study 28 in order to test the agreement between the software- and the user-selected peptides.…”

The cAMP‐PKA signalling pathway regulates hyphal growth, conidiation, trap morphogenesis, stress tolerance, and autophagy in Arthrobotrys oligospora

“…The cyclic adenosine monophosphate‐protein kinase A (cAMP‐PKA) signalling pathway is involved in various biological processes. In yeast, PKA activity modulates multiple targets, positively activating processes associated with rapid cell growth, including fermentative metabolism, ribosome biogenesis, and cell division, and negatively regulating processes associated with slow growth, such as respiratory growth and carbohydrate compound storage (Creamer et al, 2022). In budding yeast, cAMP‐PKA signalling balances respiratory activity with mitochondria‐dependent apoptosis via transcriptional regulation (Leadsham and Gourlay, 2010).…”

“…The cyclic adenosine monophosphate‐protein kinase A (cAMP‐PKA) pathway, an evolutionarily conserved signalling network, transmits extracellular stimuli and controls cellular responses through the second messenger cAMP (Kayikci and Magwene, 2018). In the absence of cAMP, PKA is inactive and exists as an asymmetric tetramer that contains a regulatory subunit dimer and two catalytic subunits (D'Souza and Heitman, 2001; Creamer et al, 2022). When a stimulatory signal is sensed, an increase in adenylate cyclase activity leads to an increase in the intracellular cAMP levels.…”

“…cAMP signalling molecules bind to the regulatory subunit of PKA (PkaR), releasing the catalytic subunit of PKA (PkaC), which in turn phosphorylates downstream targets such as other kinases and transcription factors (Toda et al, 1987a; Portela and Rossi, 2020). cAMP is hydrolysed to AMP by phosphodiesterase, and PKA returns to an inactive state as regulatory and catalytic subunits reorganize into tetramers (Creamer et al, 2022). In Saccharomyces cerevisiae , the catalytic subunit is encoded by the tpk1 , tpk2 , and tpk3 genes with different functions (Robertson and Fink, 1998; Pan and Heitman, 1999), whereas the regulatory subunit is encoded by bcy1 (Toda et al, 1987a, 1987b).…”