Projects per year
Personal profile
Area of Expertise
G protein-coupled receptors remain the single largest group of “druggable” proteins that continue to find tremendous utility in academic lab and pharmaceutical company drug-discovery programs. In 1994, Siderovski was the first to report the sequencing of a “Regulator of G protein Signaling” (RGS protein): 'G0/G1-switch gene-8' or G0S8 (subsequently renamed RGS2). Before the discovery of RGS proteins, the duration of heterotrimeric G-protein signaling was thought to be controlled solely by the intrinsic GTP hydrolysis rate of the G-alpha subunit. What Siderovski originally identified as the G0S8-homology ("GH") domain in proteins from several eukaryotic genomes (human, Drosophila melanogaster, Caenorhabditis elegans, Saccharomyces cerevisiae) is now known as the "RGS domain", a 130 amino-acid domain that contacts G-alpha switch regions to stabilize the transition state, thus accelerating GTP hydrolysis (i.e., RGS proteins act as GTPase-accelerating proteins or "GAPs" for G-alpha-GTP). Discovery of a superfamily of RGS domain-containing proteins that negatively regulate G-alpha-dependent signaling resolved a prior paradox that GPCR-stimulated signals are seen to terminate much faster in vivo than predicted from the slow GTP hydrolysis rates exhibited by purified G-alpha subunits in vitro. RGS proteins are now considered key desensitizers of heterotrimeric G protein signaling and, as such, as new drug discovery targets.
Education/Academic qualification
B.Sc.(Hons). Biochemistry, Queen's University Kingston
Ph.D. Medical Biophysics, University of Toronto
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Projects
- 15 Finished
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The role of RGS12 in differential modulation of G protein versus beta-arrestin signaling downstream of the kappa opioid receptor
SIDEROVSKI, D. & Siderovski, D.
15/02/21 → 31/12/22
Project: Research
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Enzymatic Screen for RGS Protein Modulators
Siderovski, D. & SIDEROVSKI, D. P.
National Institute on Drug Abuse
1/05/10 → 30/04/12
Project: Research
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Structural Determinants of Heterotrimeric G-protein Nucleotide Cycling
Siderovski, D. & SIDEROVSKI, D. P.
National Institute of General Medical Sciences
1/08/08 → 31/07/13
Project: Research
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Self-activating G protein α subunits engage seven-transmembrane regulator of G protein signaling (RGS) proteins and a Rho guanine nucleotide exchange factor effector in the amoeba Naegleria fowleri
Bosch, D. E., Jeck, W. R. & Siderovski, D. P., Aug 2022, In: Journal of Biological Chemistry. 298, 8, 102167.Research output: Contribution to journal › Article › peer-review
Open Access1 Scopus citations -
Contribution of HCN1 variant to sinus bradycardia: A case report
Yu, H., Gall, B., Newman, M., Hathaway, Q., Brundage, K., Ammer, A., Mathers, P., Siderovski, D. & Hull, R. W., Oct 2021, In: Journal of Arrhythmia. 37, 5, p. 1337-1347 11 p.Research output: Contribution to journal › Article › peer-review
Open Access -
Potential for Kappa-Opioid Receptor Agonists to Engineer Nonaddictive Analgesics: A Narrative Review
Kaski, S. W., White, A. N., Gross, J. D. & Siderovski, D. P., 1 Feb 2021, In: Anesthesia and analgesia. 132, 2, p. 406-419 14 p.Research output: Contribution to journal › Review article › peer-review
10 Scopus citations -
The stability of tastant detection by mouse lingual chemosensory tissue requires Regulator of G protein Signaling-21 (RGS21)
Schroer, A. B., Branyan, K. W., Gross, J. D., Chantler, P. D., Kimple, A. J., Vandenbeuch, A. & Siderovski, D. P., 2021, In: Chemical Senses. 46, bjab048.Research output: Contribution to journal › Article › peer-review
2 Scopus citations -
Erratum: Regulation of T cell activation, anxiety, and male aggression by RGS2 (Proc. Natl. Acad. Sci. U.S.A. (2000) 97 (12272–12277) DOI: 10.1073/pnas.220414397)
Oliveira-Dos-Santos, A. J., Matsumoto, G., Snow, B. E., Bai, D., Houston, F. P., Whishaw, I. Q., Mariathasan, S., Sasaki, T., Wakeham, A., Ohashi, P. S., Roder, J. C., Barnes, C. A., Siderovski, D. P. & Penninger, J. M., 6 Oct 2020, In: Proceedings of the National Academy of Sciences of the United States of America. 117, 40, p. 25182 1 p.Research output: Contribution to journal › Comment/debate
Open Access