Breadth and Specificity in Pleiotropic Protein Kinase A Activity and Environmental Responses

Frontiers in Cell and Developmental Biology

Audrey P. Gasch¹  Rachel A. Kocik² 

[1] Center for Genomic Science Innovation, University of Wisconsin-Madison, Madison, WI, United States;Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI, United States;Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, WI, United States;

关键词: protein kinase A (PKA);    spatiotemporal regulation;    cAMP microenvironments;    environmental response;    signaling specificity;   

DOI  :  10.3389/fcell.2022.803392

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown