Cdk5 Phosphorylates Dopamine D2 Receptor and Attenuates Downstream SignalingReport as inadecuate




Cdk5 Phosphorylates Dopamine D2 Receptor and Attenuates Downstream Signaling - Download this document for free, or read online. Document in PDF available to download.

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.



Author: Jaehoon Jeong, Young-Un Park, Dae-Kyum Kim, Saebom Lee, Yongdo Kwak, Seol-Ae Lee, Haeryun Lee, Yoo-Hun Suh, Yong Song Gho, Daehee

Source: http://plos.srce.hr/



DOWNLOAD PDF




Related documents