Evidence for the role of cAMP-dependent protein kinase in the down-regulation of hypothalamic HD: Reversal of cAMP-(ATP) induced inhibition of HD activity by the ‘Walsh’ inhibitor of cAMP-dependent protein kinase and by cyclic GMP

Stimulatory effects of Ca2+-CaM and PKI on partially purified hypothalamic HD (10 fold purification) have been shown under conditions involving inhibition of the enzyme by cAMP-induced phosphorylation and under control conditions. A 1:1 (v/v) mixture of 0.1 mM CaCl2 and 10 units of CaM from human red blood cells reversed the inhibition of HD induced by cAMP-dependent protein phosphorylation activity to the control level. Verapamil (0.01 mM) could partially block the former effect without affecting the control level of enzyme activity. 0.01 mM TPA did not further increase the effect of Ca2+-CaM on HD, in the presence of 0.01 mM ATP, indicating that this stimulation does not require the action of Ca2+-dependent protein kinase. The control level of HD is not influenced by 0.1 mM CaCl2 or 0.02 mM EGTA but is raised by CaM in the presence of CaCl2 (0.1 mM). A highly purified protein kinase (cAMP-dependent) inhibitor (PKI) from bovine heart and a crude inhibitor from rat cerebellum could also reverse the inhibitory effect of cAMP-dependent protein kinase under phosphorylating conditions and enhanced HD activity above control levels. PKI and Ca2+-CaM, added together, produced single, not additive effects. We conclude that cAMP-induced phosphorylation is probable the main regulatory mechanism of histamine formation and this could be influenced by both Ca2+-CaM and PKI. Inhibition of cAMP-dependent protein kinase as well as stimulation of phosphoprotein phosphatase and Ca2+-CaM-dependent phosphodiesterase might be involved in the above actions.

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Phosphorylation of pyridoxal 5′-phosphate enzymes: an intriguing and neglected topic

Rossignoli

Phillips

Astegno

et al. 2017

Amino Acids

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Pyridoxal 5'-phosphate (PLP)-dependent enzymes catalyze a wide range of reactions of amino acids and amines, with the exception of glycogen phosphorylase which exhibits peculiar both substrate preference and chemical mechanism. They represent about 4% of the gene products in eukaryotic cells. Although structure-function investigations regarding these enzymes are copious, their regulation by post-translational modifications is largely unknown. Protein phosphorylation is the most common post-translational modification fundamental in mediating diverse cellular functions. This review aims at summarizing the current knowledge on regulation of PLP enzymes by phosphorylation. Starting from the paradigmatic PLP-dependent glycogen phosphorylase, the first phosphoprotein discovered, we collect data in literature regarding functional phosphorylation events of eleven PLP enzymes belonging to different fold types and discuss the impact of the modification in affecting their activity and localization as well as the implications on the pathogenesis of diseases in which many of these enzymes are involved. The pivotal question is to correlate the structural consequences of phosphorylation among PLP enzymes of different folds with the functional modifications exerted in terms of activity or conformational changes or others. Although the literature shows that the phosphorylation of PLP enzymes plays important roles in mediating diverse cellular functions, our recapitulation of clue findings in the field makes clear that there is still much to be learnt. Besides mass spectrometry-based proteomic analyses, further biochemical and structural studies on purified native proteins are imperative to fully understand and predict how phosphorylation regulates PLP enzymes and to find the relationship between addition of a phosphate moiety and physiological response.

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Evidence for the role of cAMP-dependent protein kinase in the down-regulation of hypothalamic HD: Reversal of cAMP-(ATP) induced inhibition of HD activity by the ‘Walsh’ inhibitor of cAMP-dependent protein kinase and by cyclic GMP

Cited by 5 publications

References 7 publications

Evidence for a regulatory role of a phosphorylation-dephosphorylation cycle in hypothalamic and lung histidine decarboxylase (HisDC) activity

Evidence for a regulatory role of a phosphorylation-dephosphorylation cycle in hypothalamic and lung histidine decarboxylase (HisDC) activity

Stimulation of hypothalamic histidine decarboxylase by calcium-calmodulin and protein kinase (cAMP-dependent) inhibitor

Phosphorylation of pyridoxal 5′-phosphate enzymes: an intriguing and neglected topic

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