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dc.contributor.author
Tubio, María Rosario
dc.contributor.author
Fernández, Natalia Brenda
dc.contributor.author
Fitzsimons, Carlos Patricio
dc.contributor.author
Copsel, Sabrina Natalia
dc.contributor.author
Santiago, Sergio
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Shayo, Carina Claudia
dc.contributor.author
Davio, Carlos Alberto
dc.contributor.author
Monczor, Federico
dc.date.available
2017-04-10T14:11:20Z
dc.date.issued
2010-05-14
dc.identifier.citation
Tubio, María Rosario; Fernández, Natalia Brenda; Fitzsimons, Carlos Patricio; Copsel, Sabrina Natalia; Santiago, Sergio; et al.; Expression of a G protein-coupled receptor (GPCR) leads to attenuation of signaling by other GPCRs: experimental evidence for a spontaneous GPCR constitutive inactive form; American Society For Biochemistry And Molecular Biology; Journal Of Biological Chemistry; 285; 20; 14-5-2010; 14990-14998
dc.identifier.issn
0021-9258
dc.identifier.uri
http://hdl.handle.net/11336/15039
dc.description.abstract
The idea of G protein-coupled receptors (GPCRs) coupling to G protein solely in their active form was abolished when it was found that certain ligands induce a G protein-coupled but inactive receptor form. This receptor form interferes with signaling of other receptors by sequestering G protein. However, the spontaneous existence of this receptor species has never been established. The aim of the present work was to evaluate the existence of the spontaneous conformation of the receptor inactively coupled to G protein able to interfere with the response of other GPCRs. According to the law of mass action, receptor overexpression should lead to increased amounts of all spontaneously occurring species. Based on this, we generated Chinese hamster ovary (CHO-K1)-derived cell lines expressing various amounts of the human histamine H2 receptor. In these systems, the signaling of other endogenously and transiently expressed GPCRs was attenuated proportionally to human H2 receptor expression levels. G protein transfection specifically reverted this attenuation, strongly suggesting hijacking of the G protein from a common pool. Similar attenuation effects were observed when the β2- adrenergic receptor was overexpressed, suggesting that this is a more general phenomenon. Moreover, in human mammary MDA-MB-231 cells, a consistent increase in the response of other GPCRs was observed when endogenous expression of β2-adrenergic receptor was knocked down using specific small interfering RNAs. Our findings show that GPCRs may interact with the signaling of other receptors by modulating the availability of the G protein and suggest the existence of GPCR spontaneous coupling to G proteins in an inactive form.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Society For Biochemistry And Molecular Biology
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Receptors
dc.subject
Signal Transduction
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Histamine
dc.subject
G Protein Coupled
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Farmacología y Farmacia
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Expression of a G protein-coupled receptor (GPCR) leads to attenuation of signaling by other GPCRs: experimental evidence for a spontaneous GPCR constitutive inactive form
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-03-23T18:23:56Z
dc.identifier.eissn
1083-351X
dc.journal.volume
285
dc.journal.number
20
dc.journal.pagination
14990-14998
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Baltimore
dc.description.fil
Fil: Tubio, María Rosario. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina
dc.description.fil
Fil: Fernández, Natalia Brenda. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
dc.description.fil
Fil: Fitzsimons, Carlos Patricio. Leiden University; Países Bajos
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Fil: Copsel, Sabrina Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina
dc.description.fil
Fil: Santiago, Sergio. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina
dc.description.fil
Fil: Shayo, Carina Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina
dc.description.fil
Fil: Davio, Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); Argentina; Argentina
dc.description.fil
Fil: Monczor, Federico. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); Argentina; Argentina
dc.journal.title
Journal Of Biological Chemistry
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/285/20/14990
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1074/jbc.M109.099689
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2865266/


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