Drugs That Regulate Local Cell Signaling: AKAP Targeting as a Therapeutic Option

Cells respond to environmental cues by mobilizing signal transduction cascades that engage protein kinases and phosphoprotein phosphatases. Correct organization of these enzymes in space and time enables the efficient and precise transmission of chemical signals. The cyclic AMP-dependent protein kin...

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Bibliographic Details
Published in:Annual review of pharmacology and toxicology 2021-01, Vol.61 (1), p.361-379
Main Authors: Bucko, Paula J, Scott, John D
Format: Article
Language:English
Subjects:
A-kinase anchoring protein
anchoring disruptor agents
precision pharmacology
protein kinase A
small-molecule inhibitors
spatial signaling
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Summary:Cells respond to environmental cues by mobilizing signal transduction cascades that engage protein kinases and phosphoprotein phosphatases. Correct organization of these enzymes in space and time enables the efficient and precise transmission of chemical signals. The cyclic AMP-dependent protein kinase A is compartmentalized through its association with A-kinase anchoring proteins (AKAPs). AKAPs are a family of multivalent scaffolds that constrain signaling enzymes and effectors at subcellular locations to drive essential physiological events. More recently, it has been recognized that defective signaling in certain endocrine disorders and cancers proceeds through pathological AKAP complexes. Consequently, pharmacologically targeting these macromolecular complexes unlocks new therapeutic opportunities for a growing number of clinical indications. This review highlights recent findings on AKAP signaling in disease, particularly in certain cancers, and offers an overview of peptides and small molecules that locally regulate AKAP-binding partners.
ISSN:0362-1642
1545-4304
DOI:10.1146/annurev-pharmtox-022420-112134