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演題詳細

Poster

シナプス
Synapse

開催日 2014/9/12
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

プロテオミクス解析によるドーパミン誘導リン酸化基質の同定
Proteomic screening for substrates of protein kinases activated by dopamine stimulation

  • P2-032
  • 中牟田 信一 / Shinichi Nakamuta:1 永井 拓 / Taku Nagai:2 西岡 朋生 / Tomoki Nishioka:1 天野 睦紀 / Mutsuki Amano:1 西 昭徳 / Akinori Nishi:3 貝淵 弘三 / Kozo Kaibuchi:1 
  • 1:名古屋大院・医・神経情報薬理 / Dept. of Cell Pharmacology, Grad. Sch. of Med., Nagoya Univ. 2:名古屋大院・医・医療薬 / Dept. Neuropsychophamacol. & Hosp. Pharm., Grad. Sch. of Med., Nagoya Univ. 3:久留米大学・医・薬理学 / Dept. of Pharmacology, Sch.of Med., Kurume Univ. 

Dopamine plays a central role in the integration of neurotransmitter signaling pathways in the striatal medium spiny neurons. Dopamine activates PKA and induces the phosphorylation of DARPP-32 (phosphatase inhibitor), thereby inhibits the activity of protein phosphatase 1. This appears to induce the phosphorylation of various substrates. However, the PKA substrates downstream dopamine remains elusive. Here, we comprehensively screened phosphorylated proteins by using neostriatal slices treated with the dopamine or D1 agonist. The identities of the protein substrates and phosphorylation sites were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS) after tryptic digestion and phosphopeptide enrichment. We have identified many proteins including Rap1-GTPase activating protein (Rap1GAP) as a striatal PKA substrate. Rap1GAP is enriched in striatal medium spiny neurons and is phosphorylated by PKA at Ser-563 in response to D1 agonist. The phosphorylation sites that we identified included the site reported previously (Thomas McAvoy et al, PNAS, 2010). We here discuss the protein substrates and phosphorylation sites in dopamine signaling.

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