Aromatic l-amino acid decarboxylase phosphorylation and activation by PKGIαin vitro
2010
Duchemin, Anne-Marie | Neff, Norton H. | Hadjiconstantinou, Maria
J. Neurochem. (2010) 114, 542-552. Brain aromatic l-amino acid decarboxylase (AAAD) is subject to regulation, and phosphorylation might be involved in the short-term activation of the enzyme. Sites for serine/threonine phosphorylation are present in the deduced amino acid sequence of AAAD, and cAMP-dependent protein kinase phosphorylates and activates neuronal AAAD in vitro. We now report that cGMP-dependent protein kinase (PKG) is able to phosphorylate and activate neuronal AAAD. In an in vitro kinase assay, immunoprecipitated native and recombinant mouse brain AAAD was rapidly phosphorylated by exogenous PKGIα. When added to striatal homogenates, PKGIα increased AAAD activity in a temporal fashion similar to phosphorylation. Recombinant AAAD was also activated by the kinase demonstrating a direct effect. Native enzyme activation was moderate and characterized by increased Vmax and Km for l-DOPA. A PKG peptide inhibitor prevented AAAD phosphorylation and activation providing specificity, and causally linking the two events. Together, the findings provide evidence for PKGIα-dependent phosphorylation and activation of neuronal AAAD in vitro, and introduce AAAD as a putative PKGIα substrate. Neuronal AAAD is best known for its role in the biosynthesis of catecholamines, indoleamines and trace amines in the nervous system, and the biological importance of PKGIα phosphorylation in these processes remains to be determined.
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