Matches in SemOpenAlex for { <https://semopenalex.org/work/W2951086237> ?p ?o ?g. }
- W2951086237 abstract "Activation of G-protein coupled receptors elevates cAMP levels promoting dissociation of protein kinase A (PKA) holoenzymes and release of catalytic subunits (PKAc). This results in PKAc-mediated phosphorylation of compartmentalized substrates that control central aspects of cell physiology. The mechanism of PKAc activation and signaling have been largely characterized. However, the modes of PKAc inactivation by regulated proteolysis were unknown. Here, we identify a regulatory mechanism that precisely tunes PKAc stability and downstream signaling. Following agonist stimulation, the recruitment of the chaperone-bound E3 ligase CHIP promotes ubiquitylation and proteolysis of PKAc, thus attenuating cAMP signaling. Genetic inactivation of CHIP or pharmacological inhibition of HSP70 enhances PKAc signaling and sustains hippocampal long-term potentiation. Interestingly, primary fibroblasts from autosomal recessive spinocerebellar ataxia 16 (SCAR16) patients carrying germline inactivating mutations of CHIP show a dramatic dysregulation of PKA signaling. This suggests the existence of a negative feedback mechanism for restricting hormonally controlled PKA activities." @default.
- W2951086237 created "2019-06-27" @default.
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- W2951086237 date "2019-06-12" @default.
- W2951086237 modified "2023-10-06" @default.
- W2951086237 title "Feedback inhibition of cAMP effector signaling by a chaperone-assisted ubiquitin system" @default.
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- W2951086237 doi "https://doi.org/10.1038/s41467-019-10037-y" @default.
- W2951086237 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6561907" @default.
- W2951086237 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31189917" @default.
- W2951086237 hasPublicationYear "2019" @default.
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