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

Autor: Bucko PJ; Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA; email: bucko1@uw.edu, scottjdw@uw.edu., Scott JD; Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA; email: bucko1@uw.edu, scottjdw@uw.edu.
Jazyk: angličtina
Zdroj: Annual review of pharmacology and toxicology [Annu Rev Pharmacol Toxicol] 2021 Jan 06; Vol. 61, pp. 361-379. Date of Electronic Publication: 2020 Jul 06.
DOI: 10.1146/annurev-pharmtox-022420-112134
Abstrakt: 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.
Databáze: MEDLINE