Tyrosine hydroxylase phosphorylation increases in response to ATP and neuropeptide Y co-stimulation of ERK2 phosphorylation.
ATP and neuropeptide Y (NPY) are examples of agents co-secreted with catecholamines from neuronal and neuroendocrine cells which may regulate the function of the cells from which they are released. For example, ATP and NPY could influence chromaffin cell activity in an autocrine or paracrine manner. The primary recognized function of chromaffin cells is the synthesis and secretion of catecholamines; therefore, we hypothesize that ATP and NPY can regulate catecholamine synthesis in chromaffin cells. ATP increases phosphorylation of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, at Ser31 with a potency similar to that for ERK1/2 phosphorylation, the kinase responsible for TH phosphorylation at this site. Moreover, NPY co-stimulation increases the potency of ATP for both ERK1/2 and TH phosphorylation, while having no effect on these parameters alone. ATP and NPY had no effect on TH phosphorylation at Ser40, the primary site responsible for acute activation of the enzyme. Correspondingly, ATP and NPY did not increase TH activity. Additionally, ATP or ATP and NPY had no effect on TH expression. TH phosphorylation at Ser31 may be responsible for stabilization of the enzyme or may increase the rate and extent of phosphorylation of Ser40. We propose that ATP and NPY may serve to enhance the stimulatory effects of other agents on TH activity.
Luke
Toni M
TM
University of Nebraska Medical Center, 985800 Nebraska Medical Center, Omaha, NE, 68198-5800, USA.
Hexum
Terry D
TD
D000255:Adenosine Triphosphate / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D009478:Neuropeptide Y / Q000494:pharmacology* / Q000502:physiology; D010766:Phosphorylation; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D009478:Neuropeptide Y; D000255:Adenosine Triphosphate; D014446:Tyrosine 3-Monooxygenase; D019950:Mitogen-Activated Protein Kinase 1