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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| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_00219525_v214_n2_p181_Inda |
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todo:paper_00219525_v214_n2_p181_Inda2023-10-03T14:23:28Z Different cAMP sources are critically involved in G protein-coupled receptor CRHR1 signaling Inda, C. Claro, P.A.S. Bonfiglio, J.J. Senin, S.A. Maccarrone, G. Turck, C.W. Silberstein, S. 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00219525_v214_n2_p181_Inda |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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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 Inda, C. Claro, P.A.S. Bonfiglio, J.J. Senin, S.A. Maccarrone, G. Turck, C.W. Silberstein, S. 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. |
| format |
JOUR |
| author |
Inda, C. Claro, P.A.S. Bonfiglio, J.J. Senin, S.A. Maccarrone, G. Turck, C.W. Silberstein, S. |
| author_facet |
Inda, C. Claro, P.A.S. Bonfiglio, J.J. Senin, S.A. Maccarrone, G. Turck, C.W. Silberstein, S. |
| author_sort |
Inda, C. |
| 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 |
| url |
http://hdl.handle.net/20.500.12110/paper_00219525_v214_n2_p181_Inda |
| work_keys_str_mv |
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