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• W2144804934 endingPage "G1016" @default.
• W2144804934 startingPage "G1006" @default.
• W2144804934 abstract "The role of RhoA in myosin light-chain (MLC) 20 dephosphorylation and smooth muscle relaxation by PKA and PKG was examined in freshly dispersed and cultured smooth muscle cells expressing wild-type RhoA, constitutively active Rho V14 , and phosphorylation site-deficient Rho A188 . Activators of PKA (5,6-dichloro-1-β-ribofuranosyl benzimidazole 3′,5′-cyclic monophosphothionate, Sp-isomer; cBIMPS) or PKG [8-(4-chlorophenylthio)guanosine 3′,5′-cyclic monophosphate (8-pCPT-cGMP), sodium nitroprusside (SNP)] or both PKA and PKG (VIP) induced phosphorylation of constitutively active Rho V14 and agonist (ACh)- or GTPγS-stimulated wild-type RhoA but not Rho A188 . Phosphorylation was accompanied by translocation of membrane-bound wild-type RhoA and Rho V14 to the cytosol and complete inhibition of ACh-stimulated Rho kinase and phospholipase D activities, RhoA/Rho kinase association, MLC 20 phosphorylation, and sustained muscle contraction. Each of these events was blocked depending on the agent used, by the PKG inhibitor KT5823 or the PKA inhibitor myristoylated PKI. Inhibitors were used at a concentration (1 μM) previously shown by direct measurement of kinase activity to selectively inhibit the corresponding kinase. In muscle cells overexpressing the active phosphorylation site-deficient mutant Rho A188 , MLC 20 phosphorylation was partly inhibited by SNP, VIP, cBIMPS, and 8-pCPT-cGMP, suggesting the existence of an independent inhibitory mechanism downstream of RhoA. Results demonstrate that dephosphorylation of MLC 20 and smooth muscle relaxation are preferentially mediated by PKG- and PKA-dependent phosphorylation and inactivation of RhoA." @default.
• W2144804934 created "2016-06-24" @default.
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• W2144804934 date "2003-06-01" @default.
• W2144804934 modified "2023-10-18" @default.
• W2144804934 title "Inhibition of sustained smooth muscle contraction by PKA and PKG preferentially mediated by phosphorylation of RhoA" @default.
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• W2144804934 doi "https://doi.org/10.1152/ajpgi.00465.2002" @default.
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