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• W2944629624 abstract "Abstract Ca 2+ -transcription coupling controls gene expression patterns that define vascular smooth muscle cell (VSMC) phenotype. Although not well understood this allows normally contractile VSMCs to become proliferative following vessel injury, a process essential for repair but which also contributes to vascular remodelling, atherogenesis and restenosis. Here we show that the Ca 2+ /HCO 3 − -sensitive enzyme, soluble adenylyl cyclase (sAC), links Ca 2+ influx in human coronary artery smooth muscle cells (hCASMCs) to 3′,5′-cyclic adenosine monophosphate (cAMP) generation and phosphorylation of the transcription factor Ca 2+ /cAMP response element binding protein (CREB). Store-operated Ca 2+ entry (SOCE) into hCASMCs expressing the FRET-based cAMP biosensor H187 induced a rise in cAMP that mirrored cytosolic [Ca 2+ ]. SOCE also activated the cAMP effector, protein kinase A (PKA), as determined by the PKA reporter, AKAR4-NES, and induced phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and CREB. Transmembrane adenylyl cyclase inhibition had no effect on the SOCE-induced rise in cAMP, while sAC inhibition abolished SOCE-generated cAMP and significantly reduced SOCE-induced VASP and CREB phosphorylation. This suggests that SOCE in hCASMCs activates sAC which in turn activates the cAMP/PKA/CREB axis. sAC, which is insensitive to G-protein modulation but responsive to Ca 2+ , pH and ATP, may therefore act as an overlooked regulatory node in vascular Ca 2+ -transcription coupling." @default.
• W2944629624 created "2019-05-16" @default.
• W2944629624 creator A5010879671 @default.
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• W2944629624 date "2019-05-13" @default.
• W2944629624 modified "2023-10-16" @default.
• W2944629624 title "Soluble adenylyl cyclase links Ca2+ entry to Ca2+/cAMP-response element binding protein (CREB) activation in vascular smooth muscle" @default.
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• W2944629624 doi "https://doi.org/10.1038/s41598-019-43821-3" @default.
• W2944629624 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6514005" @default.
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• W2944629624 hasPublicationYear "2019" @default.
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