The Physiology and Pharmacology of Leucine-rich Repeat GPCRs

G protein-coupled receptors (GPCRs) represent a large and physiologically important class of cell surface receptors. There are approximately 750 known GPCRs present in the human genome that can be subdivided into general classes based upon sequence homology within their transmembrane domains. Therap...

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Prif Awduron: Brian J. Arey, James A. Dias
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Cyhoeddwyd: Frontiers Media SA 2021
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author Brian J. Arey
James A. Dias
author_browse Brian J. Arey
James A. Dias
author_facet Brian J. Arey
James A. Dias
author_sort Brian J. Arey
collection Directory of Open Access Books
description G protein-coupled receptors (GPCRs) represent a large and physiologically important class of cell surface receptors. There are approximately 750 known GPCRs present in the human genome that can be subdivided into general classes based upon sequence homology within their transmembrane domains. Therapeutically, GPCRs represent a fertile source for the development of therapies as they are a significant percentage of our current pharmacopeia. Among the three subclasses of GPCRs, the Class A (rhodopsin-like) receptors are by far the most prevalent and extensively studied. However, within the Class A receptors, sub-families of receptors can be distinguished based upon common sequence motifs within the transmembrane domains as well as extracellular and intracellular domains. One such family of Class A receptors is characterized by multiple leucine- rich repeats within their amino- terminal domains (the Leucine-rich Repeat family (LRR)). This family of GPCRs are best represented by the glycoprotein hormone receptors (LHR, FSHR and TSHR) which have been studied extensively but also includes receptors for the peptide hormone relaxin (RXFP1 and RXFP2 (RXFP2 also binds insulin-like peptide 3)) and three other receptors (LGR4, LGR5 and LGR6). LGR4-6 were, until recently, considered orphan receptors. However, emerging data have revealed that these proteins are the receptors for a family of growth factors called R-spondins. Over the last 20 years much has been learned about LRR receptors, including the development of synthetic agonists and antagonists, new insights into signaling (including signaling bias) and the physiological role these receptors play in regulating the function of many tissues. This topic will focus on what is known concerning the regulation of these receptors, their signaling pathways, functional consequences of activation and pharmacology.
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spelling doab-20.500.12854ir-562442024-03-31T13:09:47Z The Physiology and Pharmacology of Leucine-rich Repeat GPCRs Brian J. Arey James A. Dias R5-920 RC648-665 Leucine- rich repeat TSH GPCR R-spondin FSH Pharmacology LH Relaxin LRR thema EDItEUR::M Medicine and Nursing G protein-coupled receptors (GPCRs) represent a large and physiologically important class of cell surface receptors. There are approximately 750 known GPCRs present in the human genome that can be subdivided into general classes based upon sequence homology within their transmembrane domains. Therapeutically, GPCRs represent a fertile source for the development of therapies as they are a significant percentage of our current pharmacopeia. Among the three subclasses of GPCRs, the Class A (rhodopsin-like) receptors are by far the most prevalent and extensively studied. However, within the Class A receptors, sub-families of receptors can be distinguished based upon common sequence motifs within the transmembrane domains as well as extracellular and intracellular domains. One such family of Class A receptors is characterized by multiple leucine- rich repeats within their amino- terminal domains (the Leucine-rich Repeat family (LRR)). This family of GPCRs are best represented by the glycoprotein hormone receptors (LHR, FSHR and TSHR) which have been studied extensively but also includes receptors for the peptide hormone relaxin (RXFP1 and RXFP2 (RXFP2 also binds insulin-like peptide 3)) and three other receptors (LGR4, LGR5 and LGR6). LGR4-6 were, until recently, considered orphan receptors. However, emerging data have revealed that these proteins are the receptors for a family of growth factors called R-spondins. Over the last 20 years much has been learned about LRR receptors, including the development of synthetic agonists and antagonists, new insights into signaling (including signaling bias) and the physiological role these receptors play in regulating the function of many tissues. This topic will focus on what is known concerning the regulation of these receptors, their signaling pathways, functional consequences of activation and pharmacology. 2021-02-11T22:55:05Z 2021-02-11T22:55:05Z 2016-01-19 14:05:46 2016 book 18345 16648714 9782889199587 https://directory.doabooks.org/handle/20.500.12854/56244 eng Frontiers Research Topics image/jpeg Attribution 4.0 International http://www.frontiersin.org/books/The_Physiology_and_Pharmacology_of_Leucine-rich_Repeat_GPCRs/944 http://journal.frontiersin.org/researchtopic/2961/the-physiology-and-pharmacology-of-leucine-rich-repeat-gpcrs Frontiers Media SA 10.3389/978-2-88919-958-7 10.3389/978-2-88919-958-7 bf5ce210-e72e-4860-ba9b-c305640ff3ae 9782889199587 115 open access
spellingShingle R5-920
RC648-665
Leucine- rich repeat
TSH
GPCR
R-spondin
FSH
Pharmacology
LH
Relaxin
LRR
thema EDItEUR::M Medicine and Nursing
Brian J. Arey
James A. Dias
The Physiology and Pharmacology of Leucine-rich Repeat GPCRs
title The Physiology and Pharmacology of Leucine-rich Repeat GPCRs
title_full The Physiology and Pharmacology of Leucine-rich Repeat GPCRs
title_fullStr The Physiology and Pharmacology of Leucine-rich Repeat GPCRs
title_full_unstemmed The Physiology and Pharmacology of Leucine-rich Repeat GPCRs
title_short The Physiology and Pharmacology of Leucine-rich Repeat GPCRs
title_sort physiology and pharmacology of leucine rich repeat gpcrs
topic R5-920
RC648-665
Leucine- rich repeat
TSH
GPCR
R-spondin
FSH
Pharmacology
LH
Relaxin
LRR
thema EDItEUR::M Medicine and Nursing
topic_facet R5-920
RC648-665
Leucine- rich repeat
TSH
GPCR
R-spondin
FSH
Pharmacology
LH
Relaxin
LRR
thema EDItEUR::M Medicine and Nursing
url 18345
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