Ca2+ -dependent activation of tyrosine hydroxylase involves MEK1
1Department of Pharmacology, University of Melbourne, Victoria 3010, Australia.
Neuroreport
|August 28, 2001
Summary
Mitogen-activated protein kinases (MAPK) play a key role in tyrosine hydroxylase (TOH) activation. MEK1/MAPK mediates TOH activation by nicotinic receptors and calcium-increasing agonists in chromaffin cells.
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Tyrosine hydroxylase (TOH) is the rate-limiting enzyme in catecholamine synthesis.
- Acute TOH activity is regulated by phosphorylation at specific serine residues.
- Mitogen-activated protein kinases (MAPK), specifically MAPK-1 and 2, are known to phosphorylate Ser31 of TOH.
Purpose of the Study:
- To investigate the role of MEK1/MAPK in the in situ activation of TOH.
- To determine if MEK1/MAPK mediates TOH activation by nicotinic receptors and calcium influx.
Main Methods:
- Experiments were conducted using intact bovine chromaffin cells.
- TOH activity was measured following stimulation with nicotine, K+, and A23187.
- The effect of PD098059, a MEK1 inhibitor, on TOH activation was assessed.
Main Results:
- Nicotine, K+, and A23187 increased TOH activity in a calcium-dependent manner.
- PD098059 significantly reduced the activation of TOH by these agonists.
- Forskolin- and phorbol dibutyrate-induced TOH activation were not affected by PD098059.
Conclusions:
- MEK1/MAPK signaling is crucial for the acute activation of tyrosine hydroxylase.
- This pathway is involved in TOH activation triggered by nicotinic receptors and agonists that elevate intracellular calcium.
- The findings highlight a specific mechanism for regulating catecholamine synthesis in response to neuronal stimulation.
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