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Cdk5 Phosphorylates Dopamine D2 Receptor and Attenuates Downstream Signaling
The dopamine D2 receptor (DRD2) is a key receptor that mediates dopamine-associated brain functions such as mood, reward, and emotion. Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase whose function has been implicated in the brain reward circuit. In this study, we reve...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877277/ https://www.ncbi.nlm.nih.gov/pubmed/24391960 http://dx.doi.org/10.1371/journal.pone.0084482 |
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author | Jeong, Jaehoon Park, Young-Un Kim, Dae-Kyum Lee, Saebom Kwak, Yongdo Lee, Seol-Ae Lee, Haeryun Suh, Yoo-Hun Gho, Yong Song Hwang, Daehee Park, Sang Ki |
author_facet | Jeong, Jaehoon Park, Young-Un Kim, Dae-Kyum Lee, Saebom Kwak, Yongdo Lee, Seol-Ae Lee, Haeryun Suh, Yoo-Hun Gho, Yong Song Hwang, Daehee Park, Sang Ki |
author_sort | Jeong, Jaehoon |
collection | PubMed |
description | The dopamine D2 receptor (DRD2) is a key receptor that mediates dopamine-associated brain functions such as mood, reward, and emotion. Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase whose function has been implicated in the brain reward circuit. In this study, we revealed that the serine 321 residue (S321) in the third intracellular loop of DRD2 (D2i3) is a novel regulatory site of Cdk5. Cdk5-dependent phosphorylation of S321 in the D2i3 was observed in in vitro and cell culture systems. We further observed that the phosphorylation of S321 impaired the agonist-stimulated surface expression of DRD2 and decreased G protein coupling to DRD2. Moreover, the downstream cAMP pathway was affected in the heterologous system and in primary neuronal cultures from p35 knockout embryos likely due to the reduced inhibitory activity of DRD2. These results indicate that Cdk5-mediated phosphorylation of S321 inhibits DRD2 function, providing a novel regulatory mechanism for dopamine signaling. |
format | Online Article Text |
id | pubmed-3877277 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38772772014-01-03 Cdk5 Phosphorylates Dopamine D2 Receptor and Attenuates Downstream Signaling Jeong, Jaehoon Park, Young-Un Kim, Dae-Kyum Lee, Saebom Kwak, Yongdo Lee, Seol-Ae Lee, Haeryun Suh, Yoo-Hun Gho, Yong Song Hwang, Daehee Park, Sang Ki PLoS One Research Article The dopamine D2 receptor (DRD2) is a key receptor that mediates dopamine-associated brain functions such as mood, reward, and emotion. Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase whose function has been implicated in the brain reward circuit. In this study, we revealed that the serine 321 residue (S321) in the third intracellular loop of DRD2 (D2i3) is a novel regulatory site of Cdk5. Cdk5-dependent phosphorylation of S321 in the D2i3 was observed in in vitro and cell culture systems. We further observed that the phosphorylation of S321 impaired the agonist-stimulated surface expression of DRD2 and decreased G protein coupling to DRD2. Moreover, the downstream cAMP pathway was affected in the heterologous system and in primary neuronal cultures from p35 knockout embryos likely due to the reduced inhibitory activity of DRD2. These results indicate that Cdk5-mediated phosphorylation of S321 inhibits DRD2 function, providing a novel regulatory mechanism for dopamine signaling. Public Library of Science 2013-12-31 /pmc/articles/PMC3877277/ /pubmed/24391960 http://dx.doi.org/10.1371/journal.pone.0084482 Text en © 2013 Jeong et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Jeong, Jaehoon Park, Young-Un Kim, Dae-Kyum Lee, Saebom Kwak, Yongdo Lee, Seol-Ae Lee, Haeryun Suh, Yoo-Hun Gho, Yong Song Hwang, Daehee Park, Sang Ki Cdk5 Phosphorylates Dopamine D2 Receptor and Attenuates Downstream Signaling |
title | Cdk5 Phosphorylates Dopamine D2 Receptor and Attenuates Downstream Signaling |
title_full | Cdk5 Phosphorylates Dopamine D2 Receptor and Attenuates Downstream Signaling |
title_fullStr | Cdk5 Phosphorylates Dopamine D2 Receptor and Attenuates Downstream Signaling |
title_full_unstemmed | Cdk5 Phosphorylates Dopamine D2 Receptor and Attenuates Downstream Signaling |
title_short | Cdk5 Phosphorylates Dopamine D2 Receptor and Attenuates Downstream Signaling |
title_sort | cdk5 phosphorylates dopamine d2 receptor and attenuates downstream signaling |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877277/ https://www.ncbi.nlm.nih.gov/pubmed/24391960 http://dx.doi.org/10.1371/journal.pone.0084482 |
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