Regulation of Cyclin-Dependent Kinase 5 and Calcium/Calmodulin-Dependent Protein Kinase II by Phosphatidylinositol-Linked Dopamine Receptor in Rat Brain
- 1 December 2004
- journal article
- Published by Elsevier in Molecular Pharmacology
- Vol. 66 (6) , 1500-1507
- https://doi.org/10.1124/mol.104.002279
Abstract
A brain dopamine receptor that modulates phosphatidylinositol (PI) metabolism via the activation of phospholipase Cβ (PLCβ) has been described previously. The present study aims to define the downstream signaling cascade initiated by the PI-linked dopamine receptor. Incubation of rat brain frontal cortical slices with 6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959), a recently identified selective agonist of the PI-linked D1-like dopamine receptor, elicited transient time- and dose-dependent stimulations of cyclin-dependent kinase 5 (cdk5) and calcium/calmodulin-dependent protein kinase II (CaMK II) activities. The stimulation of these kinases is blocked by 20 μM R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH23390) or the PLCβ antagonist 1-[6-[[17β-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U-73122) and is attenuated by the protein kinase inhibitor calphostin C or by the intracellular calcium chelator BAPTA, indicating that SKF83959 stimulates cdk5 and CaMK II activities via a PI-linked D1-like dopamine receptor, and PLCβ and is dependent on protein kinase C and calcium. Although cdk5 and CaMK II are physically associated in native brain tissue, no change in this association was observed in response to SKF83959 stimulation or to the inhibition of either cdk5 by roscovitine or of CaMK by 2-[N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine) (KN93), suggesting that SKF83959-mediated stimulation of cdk5 or CaMK II is independent of the other kinase and that the association of the two kinases is not modulated by change of kinase activity. Moreover, we found that cdk5 phosphorylates dopamine and cAMP-regulated phosphoprotein at Thr75, whereas CaMK II is responsible for the activation of cAMP response element-binding protein in response to SKF83959 stimulation. The present data provide the first insight into the signaling mechanism for the PI-linked dopamine receptor. This information, in turn, may help in exploring the functional consequences of stimulation of this brain receptor.Keywords
This publication has 23 references indexed in Scilit:
- Cdk5: A Novel Role in Learning and MemoryNeurosignals, 2003
- A decade of CDK5Nature Reviews Molecular Cell Biology, 2001
- Regulation of cyclin-dependent kinase 5 and casein kinase 1 by metabotropic glutamate receptorsProceedings of the National Academy of Sciences, 2001
- Activation of Calcium/Calmodulin-dependent Protein Kinase IV in Long Term Potentiation in the Rat Hippocampal CA1 RegionJournal of Biological Chemistry, 2001
- SKF83959 exhibits biochemical agonism by stimulating [35S]GTPγS binding and phosphoinositide hydrolysis in rat and monkey brainNeuropharmacology, 2001
- Amplification of dopaminergic signaling by a positive feedback loopProceedings of the National Academy of Sciences, 2000
- Beyond the Dopamine ReceptorPublished by Elsevier ,1999
- CREB Phosphorylation and Dephosphorylation: A Ca2+- and Stimulus Duration–Dependent Switch for Hippocampal Gene ExpressionCell, 1996
- Effects of cAMP Simulate a Late Stage of LTP in Hippocampal CA1 NeuronsScience, 1993
- Mass measurements of inositol(1,4,5)trisphosphate in rat cerebral cortex slices using a radioreceptor assay: Effects of neurotransmitters and depolarizationBiochemical and Biophysical Research Communications, 1988