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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Inda, C., Claro, P.A.S., Bonfiglio, J.J., Senin, S.A., Maccarrone, G., Turck, C.W., Silberstein, S.
Formato: JOUR
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: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
Descripción
Sumario: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.

Ejemplares similares