Interaction Networks Explain Holoenzyme Allostery in Protein Kinase A

• Published in: Kinases and Phosphatases Vol. 1; no. 4; pp. 265 - 287
• Main Authors: Welsh, Colin L., Conklin, Abigail E., Madan, Lalima K.
• Format: Journal Article
• Language: English
• Published: 31.10.2023
• ISSN: 2813-3757; 2813-3757
• DOI: 10.3390/kinasesphosphatases1040016

Protein kinase A (PKA) signaling exemplifies phosphorylation-based signaling as we understand it today. Its catalytic-subunit structure and dynamics continue to advance our understanding of kinase mechanics as the first protein kinase catalytic domain to be identified, sequenced, cloned, and structurally detailed. The PKA holoenzyme elaborates on the role of its regulatory subunits and maintains our understanding of cAMP-dependent cellular signaling. The activation of PKA holoenzymes by cAMP is an example of specialized protein allostery, emphasizing the relevance of protein binding interfaces, unstructured regions, isoform diversity, and dynamics-based allostery. This review provides the most up-to-date overview of PKA structure and function, including a description of the catalytic and regulatory subunits’ structures. In addition, the structure, activation, and allostery of holoenzymes are covered.