Journal article
Regulator of G-protein signaling (RGS) proteins as drug targets: Progress and future potentials
The Journal of biological chemistry, Vol.294(49), pp.18571-18585
12/06/2019
DOI: 10.1074/jbc.REV119.007060
PMCID: PMC6901330
PMID: 31636120
Abstract
G protein–coupled receptors (GPCRs) play critical roles in regulating processes such as cellular homeostasis, responses to stimuli, and cell signaling. Accordingly, GPCRs have long served as extraordinarily successful drug targets. It is therefore not surprising that the discovery in the mid-1990s of a family of proteins that regulate processes downstream of GPCRs generated great excitement in the field. This finding enhanced the understanding of these critical signaling pathways and provided potentially new targets for pharmacological intervention. These regulators of G-protein signaling (RGS) proteins were viewed by many as nodes downstream of GPCRs that could be targeted with small molecules to tune signaling processes. In this review, we provide a brief overview of the discovery of RGS proteins and of the gradual and continuing discovery of their roles in disease states, focusing particularly on cancer and neurological disorders. We also discuss high-throughput screening efforts that have led to the discovery first of peptide-based and then of small-molecule inhibitors targeting a subset of the RGS proteins. We explore the unique mechanisms of RGS inhibition these chemical tools have revealed and highlight the most up–to–date studies using these tools in animal experiments. Finally, we discuss the future opportunities in the field, as there are clearly more avenues left to be explored and potentials to be realized.
Details
- Title: Subtitle
- Regulator of G-protein signaling (RGS) proteins as drug targets: Progress and future potentials
- Creators
- Joseph B O’Brien - Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa, Iowa City, Iowa 52242Joshua C Wilkinson - Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa, Iowa City, Iowa 52242David L Roman - Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.294(49), pp.18571-18585
- DOI
- 10.1074/jbc.REV119.007060
- PMID
- 31636120
- PMCID
- PMC6901330
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Elsevier Inc
- Grant note
- 5T32GM008365 / National Institutes of Health
- Alternative title
- JBC REVIEWS: RGS proteins as drug targets
- Language
- English
- Date published
- 12/06/2019
- Academic Unit
- Pharmacy; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984070687702771
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