SYNERGISTIC REGULATION OF PHOSPHOINOSITIDE 3-KINASE

磷酸肌醇3-激酶的协同调节

• 批准号: 12470502
• 负责人: HAZEKI Osamu
• 金额: $ 6.34万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470502/
• 关键词: PHOSPHOINOSITIDE 3-KINASE; INSULIN; BETAGAMMA SUBUNITS; SYNERGISM; ADENOSINE; TYROSINE KINASE; p110β; イノシトールリン脂質3キナーゼ; GTP結合タンパク質; トランスアクティベーション; 三量体型G蛋白質

The following results were obtained by establishing the Chinese hamster ovary cells stably expressing GTP-binding protein-coupled receptors, adenosine A1 receptors or fMLP receptors: (1) Adenosine orfMLP activated Akt in the cells (2) This activation was-synergistically increased by insulin (3) The effect of adenosine was abolished by treatment of the cells with pertussis toxin or transfection with beta ARK-CT peptide (4) expression of the p85 regulatory subunit of PI 3-kinase inhibited the action of adenosine (5) expression of p110beta increased markedly the action of adenosine (6) Kinase-dead p110beta prevented the action of adenosine (7) Kinase-dead p110alpha showed little effect (8) An inhibitor of tyrosine kinases inhibited the action of adenosine but a Src family-specific inhibitor PP2 had no effect (9) PP2 prevented the adenosine-induced Erk activation. These results indicated that GPCR activates Akt by a Gbetagama and p110beta-dependent pathway. Tyrosine kinase other than Src family members is also necessary for this activation.

通过建立稳定表达GTP结合蛋白偶联受体、腺苷A1受体或fMLP受体的中国仓鼠卵巢细胞，获得以下结果：（1）腺苷orfMLP激活细胞中的Akt（2）胰岛素协同增加了这种激活（3）通过用百日咳毒素处理细胞或用β ARK-CT肽转染消除了腺苷的作用（4）PI 3-激酶的p85调节亚基的表达抑制腺苷的作用（5）p110 β的表达显著增加腺苷的作用（6）激酶死亡的p110 β阻止腺苷的作用（7）激酶死亡的p110 α几乎没有影响（8）酪氨酸激酶的抑制剂抑制腺苷的作用，但Src家族-特异性抑制剂PP 2对腺苷诱导的ERK激活无影响。这些结果表明，GPCR激活Akt通过Gbetagama和p110 β依赖的途径。酪氨酸激酶以外的Src家族成员也是必要的这种激活。

项目成果

T.Hayashi et al.: "Ellagitannins from lagerstroemia speciosa as activators of glucose transport in fat cells"Planta Med.. 68. 173-175 (2002)

T.Hayashi 等人：“来自紫薇的鞣花单宁作为脂肪细胞中葡萄糖转运的激活剂”Planta Med.. 68. 173-175 (2002)

R.Kamei et al.: "Shikonin stimulates glucose uptake in 3T3L1 adipocytes via an insulin-independent tyrosine kinase pathway"Biochem. Biophys. Res. Commun.. 292. 642-651 (2002)

R.Kamei 等人：“紫草素通过不依赖于胰岛素的酪氨酸激酶途径刺激 3T3L1 脂肪细胞中的葡萄糖摄取”Biochem。

K. Hazeki et al.: "Toll-like receptor-mediated tyrosine phosphorylation of paxillin via MyD88-dependent and independent pathways."Eur. J. Immunol.. 33. 740-747 (2003)

K. Hazeki 等人：“Toll 样受体介导的桩蛋白酪氨酸磷酸化通过 MyD88 依赖性和独立途径进行。”Eur。

K.Hazeki et al.: "Toll-like receptor-mediated tyrosine phosphorylation of paxillin via MyD88-dependent and -independent pathways"Eur. J. Immunol.. 33. 740-747 (2003)

K.Hazeki 等人：“Toll 样受体介导的桩蛋白酪氨酸磷酸化通过 MyD88 依赖性和非依赖性途径”Eur。

T.Katada et al.: "Synergistic activation of a family of phosphoinositide 3-kinase via G-protein coupled and tyrosine kinase-related receptors"Chem. Phys. Lipids. 98. 79-86 (2000)

T.Katada 等人：“通过 G 蛋白偶联和酪氨酸激酶相关受体协同激活磷酸肌醇 3-激酶家族”Chem.