Phosphorylation and Activation of Tryptophan Hydroxylase by Exogenous Protein Kinase A

Abstract

The catalytic subunit of protein kinase A increases brain tryptophan hydroxylase activity. The activation is manifested as an increase in Vrnax without alterations in the Km for either tetrahydrobiopterin or tryptophan. The activation of tryptophan hydroxylase by protein kinase A is dependent on ATP and an intact kinase and is inhibited specifically by protein kinase A inhibitors. Protein kinase A also catalyzes the phosphorylation of tryptophan hydroxylase. The extent to which tryptophan hydroxylase is phosphorylated by protein kinase A is dependent on the amount of kinase used and is closely related to the degree to which the hydroxylase is activated. These results suggest that a direct relationship exists between phosphorylation and activation of tryptophan hydroxylase by protein kinase A.

Generation of the Melatonin Endocrine Message in Mammals: A Review of the Complex Regulation of Melatonin Synthesis by Norepinephrine, Peptides, and Other Pineal Transmitters

“…It may be phosphorylated by the cAMP-dependent protein kinase (PKA) (Ehret et al, 1991;Johansen et al, 1995Johansen et al, , 1996, a Ca 2ϩ /calmodulin (CaM)-dependent protein kinase (PKCa 2ϩ /CaM) (Ehret et al, 1989) and PKC (Ehret, 1994). In the pineal gland, it has been demonstrated that stimulation of PKA induces TPOH activation.…”

“…1) Activation of the cAMP/PKA pathway is the major nocturnal event that stimulates MEL synthesis Klein et al, , 1996Berg and Klein, 1971;Roseboom et al, 1996). Although the daytime levels of Tpoh mRNA and activity are elevated, activation of the cAMP/PKA pathway induces a small (13%) nocturnal increase in Tpoh gene expression, probably through the effect of P-CREB (Besançon et al, 1996 and phosphorylation/activation of TPOH (Johansen et al, 1995(Johansen et al, , 1996. These events result in a 2-fold nocturnal increase in TPOH activity (Ehret et al, 1991).…”

Disruption of the nonneuronal tph1 gene demonstrates the importance of peripheral serotonin in cardiac function

“…The enzyme is present in four structures: the pineal gland, the serotonergic neurons in the raphe nuclei that project in all brain areas, the enterochromaffin cells, and the myenteric neurons in the gut (21,22). TPH activity is modulated posttranscriptionally by phosphorylation (23)(24)(25), and protein isoforms from the brainstem and pineal gland, differing in physicochemical properties, have been identified possibly because of posttranscriptional events (26). The TPH cDNA was first isolated from rat pineal gland (27,28) and used to study the regulated expression of the tph gene (29,30).…”

Os efeitos do treinamento físico aeróbio sobre a síntese de melatonina pineal em ratos.

“…A fosforilação da TPH pode ser feita pela PKA, pela quinase dependente de cálcio e calmodulina (CaMK) e pela PKC (EHRET et al, 1989;MAITRE, 1991;JOHANSEN et al, 1995JOHANSEN et al, , 1996RIBELAYGA, 2003).…”