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• W2002242117 abstract "Corticotropin-releasing hormone (CRH) regulates diverse biological functions in mammals, through activation of two types of specific G protein-coupled receptors that are expressed as multiple mRNA spliced variants. In most cells, the type 1α CRH receptor (CRH-R1α) preferentially activates the G_s-adenylyl cyclase signaling cascade. CRH-R1α-mediated signaling activity is impaired by insertion of 29 amino acids in the first intracellular loop, a sequence modification that is characteristic of the human-specific CRH-R1β variant. In various tissues, CRH signaling events are regulated by protein kinase C (PKC). The CRH receptors contain multiple putative PKC phosphorylation sites that represent potential targets. To investigate this, we expressed recombinant CRH-R1α or CRH-R1β in human embryonic kidney 293 cells and analyzed signaling events after PKC activation. Agonist (oxytocin) or phorbol 12-myristate 13-acetate-induced activation of PKC led to phosphorylation of both CRH-R1 variants. However, CRH-R1α and CRH-R1β exhibited different functional responses to PKC-induced phosphorylation, with only the CRH-R1β susceptible to cAMP signaling desensitization. This was associated with a significant decrease of accessible CRH-R1β receptors expressed on the cell surface. Both CRH-R1 variants were susceptible to homologous desensitization and internalization following treatment with CRH; however, PKC activation increased internalization of CRH-R1β but not CRH-R1α in a β-arrestin-independent manner. Our findings indicate that CRH-R1α and -R1β exhibit differential responses to PKC-induced phosphorylation, and this might represent an important mechanism for functional regulation of CRH signaling in target cells." @default.
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• W2002242117 date "2006-09-06" @default.
• W2002242117 modified "2023-10-14" @default.
• W2002242117 title "Differential Responses of Corticotropin-Releasing Hormone Receptor Type 1 Variants to Protein Kinase C Phosphorylation" @default.
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• W2002242117 doi "https://doi.org/10.1124/jpet.106.107441" @default.
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