Breadth and Specificity in Pleiotropic Protein Kinase A Activity and Environmental Responses
Protein Kinase A (PKA) is an essential kinase that is conserved across eukaryotes and plays fundamental roles in a wide range of organismal processes, including growth control, learning and memory, cardiovascular health, and development. PKA mediates these responses through the direct phosphorylatio...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-02-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.803392/full |
| _version_ | 1828863294496047104 |
|---|---|
| author | Rachel A. Kocik Rachel A. Kocik Audrey P. Gasch Audrey P. Gasch |
| author_facet | Rachel A. Kocik Rachel A. Kocik Audrey P. Gasch Audrey P. Gasch |
| author_sort | Rachel A. Kocik |
| collection | DOAJ |
| description | Protein Kinase A (PKA) is an essential kinase that is conserved across eukaryotes and plays fundamental roles in a wide range of organismal processes, including growth control, learning and memory, cardiovascular health, and development. PKA mediates these responses through the direct phosphorylation of hundreds of proteins–however, which proteins are phosphorylated can vary widely across cell types and environmental cues, even within the same organism. A major question is how cells enact specificity and precision in PKA activity to mount the proper response, especially during environmental changes in which only a subset of PKA-controlled processes must respond. Research over the years has uncovered multiple strategies that cells use to modulate PKA activity and specificity. This review highlights recent advances in our understanding of PKA signaling control including subcellular targeting, phase separation, feedback control, and standing waves of allosteric regulation. We discuss how the complex inputs and outputs to the PKA network simultaneously pose challenges and solutions in signaling integration and insulation. PKA serves as a model for how the same regulatory factors can serve broad pleiotropic functions but maintain specificity in localized control. |
| first_indexed | 2024-12-13T03:41:09Z |
| format | Article |
| id | doaj.art-c3363b07e0a541ef8697b954b97037e2 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-13T03:41:09Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-c3363b07e0a541ef8697b954b97037e22022-12-22T00:00:57ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-02-011010.3389/fcell.2022.803392803392Breadth and Specificity in Pleiotropic Protein Kinase A Activity and Environmental ResponsesRachel A. Kocik0Rachel A. Kocik1Audrey P. Gasch2Audrey P. Gasch3Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI, United StatesLaboratory of Genetics, University of Wisconsin-Madison, Madison, WI, United StatesLaboratory of Genetics, University of Wisconsin-Madison, Madison, WI, United StatesCenter for Genomic Science Innovation, University of Wisconsin-Madison, Madison, WI, United StatesProtein Kinase A (PKA) is an essential kinase that is conserved across eukaryotes and plays fundamental roles in a wide range of organismal processes, including growth control, learning and memory, cardiovascular health, and development. PKA mediates these responses through the direct phosphorylation of hundreds of proteins–however, which proteins are phosphorylated can vary widely across cell types and environmental cues, even within the same organism. A major question is how cells enact specificity and precision in PKA activity to mount the proper response, especially during environmental changes in which only a subset of PKA-controlled processes must respond. Research over the years has uncovered multiple strategies that cells use to modulate PKA activity and specificity. This review highlights recent advances in our understanding of PKA signaling control including subcellular targeting, phase separation, feedback control, and standing waves of allosteric regulation. We discuss how the complex inputs and outputs to the PKA network simultaneously pose challenges and solutions in signaling integration and insulation. PKA serves as a model for how the same regulatory factors can serve broad pleiotropic functions but maintain specificity in localized control.https://www.frontiersin.org/articles/10.3389/fcell.2022.803392/fullprotein kinase A (PKA)spatiotemporal regulationcAMP microenvironmentsenvironmental responsesignaling specificity |
| spellingShingle | Rachel A. Kocik Rachel A. Kocik Audrey P. Gasch Audrey P. Gasch Breadth and Specificity in Pleiotropic Protein Kinase A Activity and Environmental Responses Frontiers in Cell and Developmental Biology protein kinase A (PKA) spatiotemporal regulation cAMP microenvironments environmental response signaling specificity |
| title | Breadth and Specificity in Pleiotropic Protein Kinase A Activity and Environmental Responses |
| title_full | Breadth and Specificity in Pleiotropic Protein Kinase A Activity and Environmental Responses |
| title_fullStr | Breadth and Specificity in Pleiotropic Protein Kinase A Activity and Environmental Responses |
| title_full_unstemmed | Breadth and Specificity in Pleiotropic Protein Kinase A Activity and Environmental Responses |
| title_short | Breadth and Specificity in Pleiotropic Protein Kinase A Activity and Environmental Responses |
| title_sort | breadth and specificity in pleiotropic protein kinase a activity and environmental responses |
| topic | protein kinase A (PKA) spatiotemporal regulation cAMP microenvironments environmental response signaling specificity |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.803392/full |
| work_keys_str_mv | AT rachelakocik breadthandspecificityinpleiotropicproteinkinaseaactivityandenvironmentalresponses AT rachelakocik breadthandspecificityinpleiotropicproteinkinaseaactivityandenvironmentalresponses AT audreypgasch breadthandspecificityinpleiotropicproteinkinaseaactivityandenvironmentalresponses AT audreypgasch breadthandspecificityinpleiotropicproteinkinaseaactivityandenvironmentalresponses |