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Activation of aromatic l ‐amino acid decarboxylase by calcium/calmodulin kinase II
Author(s) -
Neff N. H.,
Duchemin AM.,
Hadjiconstantinou Maria
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.38_6.x
Subject(s) - biochemistry , aromatic l amino acid decarboxylase , kinase , phosphorylation , calmodulin , tyrosine hydroxylase , enzyme , protein kinase a , tyrosine , chemistry , enzyme activator , biology
Calcium/calmodulin‐dependent protein kinase II (CAMKII) is widely distributed in the brain, and is involved in the regulation of neurotransmitter synthesis. Tyrosine hydroxylase and tryptophan hydroxylase, the two enzymes involved in the first step in the synthesis of catecholamines and indolamines, respectively, are phosphorylated by CAMKII. We now found that aromatic l ‐amino acid decarboxylase (AAAD), the common second enzyme of both synthetic pathways, is activated by CAMKII. AAAD activity was assayed in mouse striatum homogenates with L ‐DOPA as a substrate. The activation of AAAD by CAMKII in vitro is time and concentration‐dependent with maximal activity observed with 1.5 μg/mL of purified brain CAMKII and a 20‐min incubation. CAMKII induces a 30% increase of the apparent Vmax of the enzyme without changing its affinity for L ‐DOPA and the cofactor pyridoxal‐5′‐phosphate. We have previously shown that AAAD can be phosphorylated by cyclic AMP‐and cyclic GMP‐dependent protein kinases. These two kinases induced an increase of AAAD activity of about 20%. Phosphorylation by several differentially regulated serine‐threonine kinases might be the mechanism responsible for the short‐term kinetic activation of the enzyme, which has been found in vivo after physiological stimuli and neurotransmitter receptor modulation. Acknowledgements: Supported, in part, by grant NS34571.