| Project/Area Number |
08458251
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | University of Tokyo |
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Principal Investigator |
HAGA Tatsuya University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (30011646)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1997: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1996: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Keywords | G Protein / G Protein-Coupled Receptor / Desensitization / Muscarinic Receptor / G Protein-Coupled Receptor Kinases / Dopamine Receptor / Acetylcholine Receptor / Internalization / 受容体キナーゼ / リン酸化 / エンドサイトーシス |
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| Research Abstract |
We have examined the relation between phosphorylation by G protein-coupled receptor kinases (GRK) of G protein-coupled receptors and their desensitization, particularly on muscarinic acetylcholine receptor m2 subtypes (m2 receptors) expressed in cultured cells. We found that internalization, down-regulation and uncoupling of m2 receptors expressed in chinese hamster ovary cells (CHO cells) were facilitated by coexpression of GRK2, most probably through agonist-dependent phosphorylation of m2 receptors. Internalization of other G protein-coupled receptors including m3, m4 and m5 muscarinic and dopamine D2 receptors, which were expressed in COS-7 cells, was also found to be facilitated by coexpression of GRK2, whereas internalization of m1 muscarinic and dopamine D4 receptors was not facilitated by coexpression of GRK2.
Activation of GRK2 by agonist-bound receptros and G protein betagamma subunits was found to be attenuated by calmodulin in a Ca^<2+> dependent manner. Tubulin was found to interact with and be phosphorylated by GRK2, in spite of the fact that the substrate specificity of GRK2 is very strict and the known substrates are limited to activated forms of G protein-coupled receptors. Physiological meanings of inhibition by calmodulin and tubulin phosphorylation remain to be elucidated.
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