Protein kinase C mediates phosphorylation, desensitization, and trafficking of the D2 dopamine receptor

The Journal of Biological Chemistry
Yoon Namkung, David R Sibley

Abstract

Previously, D2 dopamine receptors (D2 DARs) have been shown to undergo G-protein-coupled receptor kinase phosphorylation in an agonist-specific fashion. We have now investigated the ability of the second messenger-activated protein kinases, protein kinase A (PKA) and protein kinase C (PKC), to mediate phosphorylation and desensitization of the D2 DAR. HEK293T cells were transiently transfected with the D2 DAR and then treated with intracellular activators and inhibitors of PKA or PKC. Treatment with agents that increase cAMP, and activate PKA, had no effect on the phosphorylation state of the D2 DAR, suggesting that PKA does not phosphorylate the D2 DAR in HEK293T cells. In contrast, cellular treatment with phorbol 12-myristate 13-acetate (PMA), a PKC activator, resulted in an approximately 3-fold increase in D2 DAR phosphorylation. The phosphorylation was specific for PKC as the PMA effect was mimicked by phorbol 12,13-dibutyrate, but not by 4alpha-phorbol 12,13-didecanoate, active and inactive, phorbol diesters, respectively. The PMA-mediated D2 DAR phosphorylation was completely blocked by co-treatment with the PKC inhibitor, bisindolylmaleimide II, and augmented by co-transfection with PKCbetaI. In contrast, PKC inhibition ...Continue Reading

References

Mar 29, 1994·Proceedings of the National Academy of Sciences of the United States of America·G PeiR J Lefkowitz
Aug 1, 1993·The Journal of Cell Biology·A M van der BliekS L Schmid
Aug 18, 1997·Biochemical and Biophysical Research Communications·J E Lachowicz, D R Sibley
Aug 28, 1998·Current Opinion in Cell Biology·S L SchmidP De Camilli
Jul 17, 1999·European Journal of Biochemistry·K IwataT Haga
Apr 29, 2000·Trends in Pharmacological Sciences·K J WayG L King
Sep 12, 2000·The Journal of Comparative Neurology·M U NaikT C Sacktor
Sep 26, 2000·American Journal of Physiology. Cell Physiology·K S MurthyG M Makhlouf
Oct 24, 2000·The Journal of Biological Chemistry·C KraselM J Lohse
May 25, 2001·The Journal of Biological Chemistry·M ScarselliR Maggio
Aug 25, 2001·Journal of Neurochemistry·R WageyC Krieger
Dec 24, 2002·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Ernest P Noble
Apr 19, 2003·Cellular Signalling·José Vázquez-PradoJ Adolfo García-Sáinz
Apr 30, 2003·Neuron·Raul R GainetdinovRichard T Premont
Nov 20, 2003·Journal of Cell Science·Wesley K KroezeBryan L Roth
Dec 4, 2003·Progress in Neuro-psychopharmacology & Biological Psychiatry·Shitij Kapur, David Mamo
Jan 28, 2004·Annual Review of Pharmacology and Toxicology·Alan WiseStephen Rees
May 12, 2004·Biochemical Pharmacology·Elizabeth Akam, Philip G Strange
Jun 26, 2004·Annual Review of Neuroscience·Raul R GainetdinovMarc G Caron

❮ Previous
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Citations

Oct 12, 2005·Pflügers Archiv : European journal of physiology·Hjalmar BrismarUlla Holtbäck
Nov 6, 2010·Archives of Pharmacal Research·Dong Im ChoKyeong-Man Kim
Jan 21, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Simona PerraHitoshi Morikawa
Oct 7, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Sudarat NimitvilaiMark S Brodie
Jan 5, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Elisabeth BarbierJia Bei Wang
Mar 2, 2010·Médecine sciences : M/S·Dominic ThibaultLouis-Eric Trudeau
Jan 15, 2011·The Journal of Biological Chemistry·Dominic ThibaultLouis-Éric Trudeau
Nov 6, 2008·The Journal of Biological Chemistry·Lisa A HazelwoodDavid R Sibley
Feb 19, 2010·The Journal of Pharmacology and Experimental Therapeutics·Sudarat Nimitvilai, Mark S Brodie
Oct 15, 2009·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Yasukazu HozumiKaoru Goto
Dec 3, 2011·Endocrine-related Cancer·Federico Gatto, Leo J Hofland
Apr 7, 2007·European Journal of Endocrinology·Rosario PivonelloLeo J Hofland
Dec 20, 2015·Journal of Neurochemistry·Nathalie SchmiegClotilde Mannoury la Cour
Oct 24, 2008·Journal of Receptor and Signal Transduction Research·Ok-Jin Kim
Apr 19, 2008·European Journal of Pharmacology·Sokhom S Pin, Ben A Bahr
Nov 11, 2008·Annals of the New York Academy of Sciences·Anna M Lee, Robert O Messing
Nov 23, 2006·The European Journal of Neuroscience·C JompheL-E Trudeau
Sep 5, 2007·Journal of Neurochemistry·Irit Itzhaki Van-HamPaul R Albert
Dec 7, 2007·British Journal of Pharmacology·E KellyG Henderson
Oct 26, 2010·Journal of Neurochemistry·Michele L Rankin, David R Sibley
Mar 22, 2016·ACS Chemical Neuroscience·Alexander G ZestosMargaret E Gnegy
Sep 5, 2006·Prostaglandins, Leukotrienes, and Essential Fatty Acids·Robert K McNamara, Susan E Carlson
Feb 8, 2006·Pharmacology & Therapeutics·Vsevolod V Gurevich, Eugenia V Gurevich

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