1989 Fiscal Year Final Research Report Summary
Physiological roles of GTP binding protein associated with pertussis toxin (IAP) for the study of medicinal and diagnostic functions
| Project/Area Number |
61870093
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Hokkaido University |
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Principal Investigator |
TOKUMITSU Yukiko Faculty of Pharmaceutical Sciences, Hokkaido University, 薬学部, 助教授 (60001046)
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| Co-Investigator(Kenkyū-buntansha) |
UI Michio Faculty of Pharmaceutical Sciences, Tokyo University, 薬学部, 教授 (50001037)
KAMATAKI Tetsuya Faculty of Pharmaceutical Sciences, Hokkaido University, 薬学部, 教授 (00009177)
MURAYAMA Toshihiko Faculty of Pharmaceutical Sciences, Hokkaido University, 薬学部, 助手 (90174317)
OKADA Fumihiko Health Center, Hokkaido University, 保健管理センター, 助教授 (40109517)
NOMURA Yasuyuki Faculty of Pharmaceutical Sciences, Hokkaido University, 薬学部, 教授 (00034041)
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| Project Period (FY) |
1986 – 1988
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| Keywords | IAP / GTP binding protein / Proliferation and differentiation of cells / Phospholipase A_2 / Signal transduction / NIH3T3^<ras> / Adenylate cyclase system |
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| Research Abstract |
Many kinds of hormones and neurotransmitters interact with their specific receptors coupled to guanine nucleotide-binding protein (G protein) and lead to physiological actions. Pertussis toxin (IAP) lose their function of G protein in various types of cells. IAP is a useful probe to study the mechanism of signal transduction via G protein. Therefore, we examined the roles of G protein serving as IAP substrates and other G protein. The results obtained were as follows. (1) Serum-induced DNA synthesis in 3T3 fibroblasts was inhibited via loss of function of IAP substrates, thereby leading to cell proliferation. (2) IAP-sensitive G protein plays a role in c-myc gene expression of rat hepatocytes. (3) A new G protein sensitive to IAP was induced during differentiation of HL-60 cells into neutrophil type of cells. (4) IAP inhibited differentiation of 3T3L1 cells into adipocytes via IAP-sensitive G protein. (5) One of two types of the P2-purinergic receptors was coupled to IAP-sensitive G protein, resulting in inhibition of cAMP formation. (6) Adenylate cyclase activity in NIH-3T3^<src> cells decreased via reduction of the number of beta-adrenoceptors and phosphorylation of Gs protein but not ADP-ribosylation of Gi or Go. (7) Thrombin and epinephrine in platelets activated phospholipase A2 via IAP-sensitive G protein. (8) Adenylate cyclase activity in NIH-3T3^<ras> cells increased via rbduction of the amount of IAP-sensitive G protein. (9) Purified muscarinic receptors were coupled to purified IAP-sensitive G protein reconstituted. (10) Serotonin 1A receptors were coupled to IAP-sensitive G protein in rat brain cortex and hippocampus. (11) Amino acid sequences were determined, and GTP-binding sites and ADP-ribosylation sites were identified by molecular cloning of rat brain Gi and Go cDNA.
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