δείτε την πρωτότυπη σελίδα τεκμηρίου στον ιστότοπο του αποθετηρίου του φορέα για περισσότερες πληροφορίες και για να δείτε όλα τα ψηφιακά αρχεία του τεκμηρίου*
Protein kinase G phosphorylates soluble guanylyl cyclase on serine 64
and inhibits its activity
Zhou, Zongmin
Sayed, Nazish
Pyriochou, Anastasia
Roussos,
Charis
Fulton, David
Beuve, Annie
Papapetropoulos, Andreas
Objective - Binding of nitric oxide (NO) to soluble guanylyl cyclase
(sGC) leads to increased cGMP synthesis that activates cGMP-dependent
protein kinase (PKG). Herein, we tested whether sGC activity is
regulated by PKG.
Methods and Results - Overexpression of a constitutively active form of
PKG (Delta PKG) stimulated P-32 incorporation into the alpha 1 subunit.
Serine to alanine mutation of putative sites revealed that Ser64 is the
main phosphorylation site for PKG. Using a phospho-specific antibody we
observed that endogenous sGC phosphorylation on Ser 64 increases in
cells and tissues exposed to NO, in a PKG-inhibitable manner. Wild-type
(wt) sGC coexpressed with Delta PKG exhibited lower basal and
NO-stimulated cGMP accumulation, whereas the S64A alpha 1/beta 1 sGC was
resistant to the PKG-induced reduction in activity. Using purified sGC
we observed that the S64D alpha 1 phosphomimetic/beta 1 dimer exhibited
lower Vmax; moreover, the decrease in Km after NO stimulation was less
pronounced in S64D alpha 1/beta 1 compared to wild-type sGC. Expression
of a phosphorylation-deficient sGC showed enhanced responsiveness to
endothelium-derived NO, reduced desensitization to acute NO exposure,
and allowed for greater VASP phosphorylation.
Conclusions - We conclude that PKG phosphorylates sGC on Ser64 of the
alpha 1 subunit and that phosphorylation inhibits sGC activity,
establishing a negative feedback loop.
(EN)
*Η εύρυθμη και αδιάλειπτη λειτουργία των διαδικτυακών διευθύνσεων των συλλογών (ψηφιακό αρχείο, καρτέλα τεκμηρίου στο αποθετήριο) είναι αποκλειστική ευθύνη των αντίστοιχων Φορέων περιεχομένου.
Protein kinase G phosphorylates soluble guanylyl cyclase on serine 64 and inhibits its activity
Protein kinase G phosphorylates soluble guanylyl cyclase on serine 64 and inhibits its activity
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