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Historical review: a brief history and personal retrospective of seven-transmembrane receptors.

Publication ,  Journal Article
Lefkowitz, RJ
Published in: Trends Pharmacol Sci
August 2004

Pharmacologists have studied receptors for more than a century but a molecular understanding of their properties has emerged only during the past 30-35 years. In this article, I provide a personal retrospective of how developments and discoveries primarily during the 1970s and 1980s led to current concepts about the largest group of receptors, the superfamily of seven-transmembrane (7TM) receptors [also known as G-protein-coupled receptors (GPCRs)]. Significant technical advances such as the development of methods for radioligand binding, solubilization and purification of the beta(2)-adrenoceptor and other adrenoceptors led to the cloning of receptor genes and the discovery of their 7TM architecture and homology with rhodopsin. A universal mechanism of receptor regulation by G-protein-coupled receptor kinases (GRKs) and arrestins, originally discovered as a means of "desensitizing" G-protein-mediated second-messenger generation, was subsequently found to mediate both receptor endocytosis and activation of a growing list of signaling pathways such as those involving mitogen-activated protein kinases. Numerous opportunities for novel therapeutics should emerge from current and future research on 7TM receptor biology.

Duke Scholars

Published In

Trends Pharmacol Sci

DOI

ISSN

0165-6147

Publication Date

August 2004

Volume

25

Issue

8

Start / End Page

413 / 422

Location

England

Related Subject Headings

  • Receptors, G-Protein-Coupled
  • Pharmacology & Pharmacy
  • Membrane Proteins
  • Humans
  • History, 20th Century
  • Animals
  • 3214 Pharmacology and pharmaceutical sciences
  • 11 Medical and Health Sciences
  • 06 Biological Sciences
 

Citation

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Lefkowitz, R. J. (2004). Historical review: a brief history and personal retrospective of seven-transmembrane receptors. Trends Pharmacol Sci, 25(8), 413–422. https://doi.org/10.1016/j.tips.2004.06.006
Lefkowitz, Robert J. “Historical review: a brief history and personal retrospective of seven-transmembrane receptors.Trends Pharmacol Sci 25, no. 8 (August 2004): 413–22. https://doi.org/10.1016/j.tips.2004.06.006.
Lefkowitz, Robert J. “Historical review: a brief history and personal retrospective of seven-transmembrane receptors.Trends Pharmacol Sci, vol. 25, no. 8, Aug. 2004, pp. 413–22. Pubmed, doi:10.1016/j.tips.2004.06.006.
Journal cover image

Published In

Trends Pharmacol Sci

DOI

ISSN

0165-6147

Publication Date

August 2004

Volume

25

Issue

8

Start / End Page

413 / 422

Location

England

Related Subject Headings

  • Receptors, G-Protein-Coupled
  • Pharmacology & Pharmacy
  • Membrane Proteins
  • Humans
  • History, 20th Century
  • Animals
  • 3214 Pharmacology and pharmaceutical sciences
  • 11 Medical and Health Sciences
  • 06 Biological Sciences