Matches in SemOpenAlex for { <https://semopenalex.org/work/W4317478839> ?p ?o ?g. }
- W4317478839 abstract "cAMP, a key player in many physiological processes, was classically considered to originate solely from the plasma membrane (PM). This view was recently challenged by observations showing that upon internalization GsPCRs can sustain signaling from endosomes and/or the trans-Golgi network (TGN). In this new view, after the first PM-generated cAMP wave, the internalization of GsPCRs and ACs generates a second wave that was strictly associated with nuclear transcriptional events responsible for triggering specific biological responses. Here, we report that the endogenously expressed TSHR, a canonical GsPCR, triggers an internalization-dependent, calcium-mediated nuclear sAC activation that drives PKA activation and CREB phosphorylation. Both pharmacological and genetic sAC inhibition, which did not affect the cytosolic cAMP levels, blunted nuclear cAMP accumulation, PKA activation, and cell proliferation, while an increase in nuclear sAC expression significantly enhanced cell proliferation. Furthermore, using novel nuclear-targeted optogenetic actuators, we show that light-stimulated nuclear cAMP synthesis can mimic the proliferative action of TSH by activating PKA and CREB. Therefore, based on our results, we propose a novel three-wave model in which the “third” wave of cAMP is generated by nuclear sAC. Despite being downstream of events occurring at the PM (first wave) and endosomes/TGN (second wave), the nuclear sAC-generated cAMP (third wave) is sufficient and rate-limiting for thyroid cell proliferation." @default.
- W4317478839 created "2023-01-20" @default.
- W4317478839 creator A5005283346 @default.
- W4317478839 creator A5046585818 @default.
- W4317478839 creator A5077419111 @default.
- W4317478839 creator A5080179082 @default.
- W4317478839 date "2023-01-19" @default.
- W4317478839 modified "2023-09-28" @default.
- W4317478839 title "Soluble cyclase-mediated nuclear cAMP synthesis is sufficient for cell proliferation" @default.
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