Different cAMP sources are critically involved in G protein-coupled receptor CRHR1 signaling

Corticotropin-releasing hormone receptor 1 (CRHR1) activates G protein-dependent and internalization-dependent signaling mechanisms. Here, we report that the cyclic AMP (cAMP) response of CRHR1 in physiologically relevant scenarios engages separate cAMP sources, involving the atypical soluble adenyl...

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Autor principal:	Bonfiglio, Juan José
Publicado:	2016
Materias:	adenylate cyclase corticotropin releasing factor receptor 1 cyclic AMP G protein coupled receptor mitogen activated protein kinase 3 bicarbonate calcium corticotropin releasing factor corticotropin releasing factor receptor cyclic AMP dependent protein kinase guanine nucleotide exchange factor animal cell Article cell interaction controlled study endocytosis enzyme activation enzyme activity nonhuman priority journal protein expression signal transduction 3T3-L1 cell line ACTH secreting cell animal cell membrane drug effects enzymology human metabolism mouse rat solubility 3T3-L1 Cells Adenylyl Cyclases Animals Bicarbonates Calcium Cell Membrane Corticotrophs Corticotropin-Releasing Hormone Cyclic AMP Cyclic AMP-Dependent Protein Kinases Endocytosis Guanine Nucleotide Exchange Factors Humans Mice Rats Receptors, Corticotropin-Releasing Hormone Signal Transduction Solubility
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219525_v214_n2_p181_Inda http://hdl.handle.net/20.500.12110/paper_00219525_v214_n2_p181_Inda
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_00219525_v214_n2_p181_Inda
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spelling	paper:paper_00219525_v214_n2_p181_Inda2023-06-08T14:43:40Z Different cAMP sources are critically involved in G protein-coupled receptor CRHR1 signaling Bonfiglio, Juan José adenylate cyclase corticotropin releasing factor receptor 1 cyclic AMP G protein coupled receptor mitogen activated protein kinase 3 adenylate cyclase bicarbonate calcium corticotropin releasing factor corticotropin releasing factor receptor corticotropin releasing factor receptor 1 cyclic AMP cyclic AMP dependent protein kinase guanine nucleotide exchange factor animal cell Article cell interaction controlled study endocytosis enzyme activation enzyme activity nonhuman priority journal protein expression signal transduction 3T3-L1 cell line ACTH secreting cell animal cell membrane drug effects enzymology human metabolism mouse rat solubility 3T3-L1 Cells Adenylyl Cyclases Animals Bicarbonates Calcium Cell Membrane Corticotrophs Corticotropin-Releasing Hormone Cyclic AMP Cyclic AMP-Dependent Protein Kinases Endocytosis Guanine Nucleotide Exchange Factors Humans Mice Rats Receptors, Corticotropin-Releasing Hormone Signal Transduction Solubility Corticotropin-releasing hormone receptor 1 (CRHR1) activates G protein-dependent and internalization-dependent signaling mechanisms. Here, we report that the cyclic AMP (cAMP) response of CRHR1 in physiologically relevant scenarios engages separate cAMP sources, involving the atypical soluble adenylyl cyclase (sAC) in addition to transmembrane adenylyl cyclases (tmACs). cAMP produced by tmACs and sAC is required for the acute phase of extracellular signal regulated kinase 1/2 activation triggered by CRH-stimulated CRHR1, but only sAC activity is essential for the sustained internalization-dependent phase. Thus, different cAMP sources are involved in different signaling mechanisms. Examination of the cAMP response revealed that CRH-activated CRHR1 generates cAMP after endocytosis. Characterizing CRHR1 signaling uncovered a specific link between CRH-activated CRHR1, sAC, and endosome-based signaling. We provide evidence of sAC being involved in an endocytosis-dependent cAMP response, strengthening the emerging model of GPCR signaling in which the cAMP response does not occur exclusively at the plasma membrane and introducing the notion of sAC as an alternative source of cAMP. © 2016 Inda et al. Fil:Bonfiglio, J.J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219525_v214_n2_p181_Inda http://hdl.handle.net/20.500.12110/paper_00219525_v214_n2_p181_Inda
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	adenylate cyclase corticotropin releasing factor receptor 1 cyclic AMP G protein coupled receptor mitogen activated protein kinase 3 adenylate cyclase bicarbonate calcium corticotropin releasing factor corticotropin releasing factor receptor corticotropin releasing factor receptor 1 cyclic AMP cyclic AMP dependent protein kinase guanine nucleotide exchange factor animal cell Article cell interaction controlled study endocytosis enzyme activation enzyme activity nonhuman priority journal protein expression signal transduction 3T3-L1 cell line ACTH secreting cell animal cell membrane drug effects enzymology human metabolism mouse rat solubility 3T3-L1 Cells Adenylyl Cyclases Animals Bicarbonates Calcium Cell Membrane Corticotrophs Corticotropin-Releasing Hormone Cyclic AMP Cyclic AMP-Dependent Protein Kinases Endocytosis Guanine Nucleotide Exchange Factors Humans Mice Rats Receptors, Corticotropin-Releasing Hormone Signal Transduction Solubility
spellingShingle	adenylate cyclase corticotropin releasing factor receptor 1 cyclic AMP G protein coupled receptor mitogen activated protein kinase 3 adenylate cyclase bicarbonate calcium corticotropin releasing factor corticotropin releasing factor receptor corticotropin releasing factor receptor 1 cyclic AMP cyclic AMP dependent protein kinase guanine nucleotide exchange factor animal cell Article cell interaction controlled study endocytosis enzyme activation enzyme activity nonhuman priority journal protein expression signal transduction 3T3-L1 cell line ACTH secreting cell animal cell membrane drug effects enzymology human metabolism mouse rat solubility 3T3-L1 Cells Adenylyl Cyclases Animals Bicarbonates Calcium Cell Membrane Corticotrophs Corticotropin-Releasing Hormone Cyclic AMP Cyclic AMP-Dependent Protein Kinases Endocytosis Guanine Nucleotide Exchange Factors Humans Mice Rats Receptors, Corticotropin-Releasing Hormone Signal Transduction Solubility Bonfiglio, Juan José Different cAMP sources are critically involved in G protein-coupled receptor CRHR1 signaling
topic_facet	adenylate cyclase corticotropin releasing factor receptor 1 cyclic AMP G protein coupled receptor mitogen activated protein kinase 3 adenylate cyclase bicarbonate calcium corticotropin releasing factor corticotropin releasing factor receptor corticotropin releasing factor receptor 1 cyclic AMP cyclic AMP dependent protein kinase guanine nucleotide exchange factor animal cell Article cell interaction controlled study endocytosis enzyme activation enzyme activity nonhuman priority journal protein expression signal transduction 3T3-L1 cell line ACTH secreting cell animal cell membrane drug effects enzymology human metabolism mouse rat solubility 3T3-L1 Cells Adenylyl Cyclases Animals Bicarbonates Calcium Cell Membrane Corticotrophs Corticotropin-Releasing Hormone Cyclic AMP Cyclic AMP-Dependent Protein Kinases Endocytosis Guanine Nucleotide Exchange Factors Humans Mice Rats Receptors, Corticotropin-Releasing Hormone Signal Transduction Solubility
description	Corticotropin-releasing hormone receptor 1 (CRHR1) activates G protein-dependent and internalization-dependent signaling mechanisms. Here, we report that the cyclic AMP (cAMP) response of CRHR1 in physiologically relevant scenarios engages separate cAMP sources, involving the atypical soluble adenylyl cyclase (sAC) in addition to transmembrane adenylyl cyclases (tmACs). cAMP produced by tmACs and sAC is required for the acute phase of extracellular signal regulated kinase 1/2 activation triggered by CRH-stimulated CRHR1, but only sAC activity is essential for the sustained internalization-dependent phase. Thus, different cAMP sources are involved in different signaling mechanisms. Examination of the cAMP response revealed that CRH-activated CRHR1 generates cAMP after endocytosis. Characterizing CRHR1 signaling uncovered a specific link between CRH-activated CRHR1, sAC, and endosome-based signaling. We provide evidence of sAC being involved in an endocytosis-dependent cAMP response, strengthening the emerging model of GPCR signaling in which the cAMP response does not occur exclusively at the plasma membrane and introducing the notion of sAC as an alternative source of cAMP. © 2016 Inda et al.
author	Bonfiglio, Juan José
author_facet	Bonfiglio, Juan José
author_sort	Bonfiglio, Juan José
title	Different cAMP sources are critically involved in G protein-coupled receptor CRHR1 signaling
title_short	Different cAMP sources are critically involved in G protein-coupled receptor CRHR1 signaling
title_full	Different cAMP sources are critically involved in G protein-coupled receptor CRHR1 signaling
title_fullStr	Different cAMP sources are critically involved in G protein-coupled receptor CRHR1 signaling
title_full_unstemmed	Different cAMP sources are critically involved in G protein-coupled receptor CRHR1 signaling
title_sort	different camp sources are critically involved in g protein-coupled receptor crhr1 signaling
publishDate	2016
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219525_v214_n2_p181_Inda http://hdl.handle.net/20.500.12110/paper_00219525_v214_n2_p181_Inda
work_keys_str_mv	AT bonfigliojuanjose differentcampsourcesarecriticallyinvolvedingproteincoupledreceptorcrhr1signaling
_version_	1768544806989987840

Different cAMP sources are critically involved in G protein-coupled receptor CRHR1 signaling

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