Studies of protein phophatases on immune response in normal and autoimmune disease mice.

蛋白磷酸酶对正常和自身免疫性疾病小鼠免疫反应的研究。

• 批准号: 04454164
• 负责人: KIKUCHI Kunimi
• 金额: $ 0.64万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454164/
• 关键词: Protein phosphatase; Autoimmune disease; Immune respose; CTLL-2; IL-2; PP1; Protein dephosphorylation; Signal transduction; プロテインホスフアターゼ; セリン; スレオニン ホスフアターゼ; チロシンホスフアターゼ; MRL; 1prマウス; PP2A; PP2B; PP2C

Activities of protein phophatases PP1 and PP2A were determined in T and B Iymphocytes of autoimmune-prone MRL/MpJ-1pr/1pr mice (MRL/1pr mice) and two control strains, MRL/MpJ-+/+ mice (MRL/+/+ mice) and C3H/HeJ mice. Potential PP1 activity, which was measured after treatment of lymphocytes with Co^<2+>-trypsin, was much higher in T lymphocytes than B lymphocytes. However, no difference in the activity was observed between MRL/1pr mice and the controls. Spontaneous PP2A activity showed similar levels in T and B lymphocytes from normal mice but potential PP2A activity which was measured after treatment with 2-mercaptoethanol, was significantly higher in T lymphocytes from MRL/1pr mice than those from controls. No differences were detected in PP1 or PP2A activities in B lymphocytes.In the IL-2-dependent murine cytotoxic T cell line CTLL-2, IL-2 induced a rapid and transient decrease in Co^<2+>-trypsin-treated activity of protein phosphatase PP1. The PP1 activity declined to a minimum level, being 70% of control value within 45 min. The decrease of PP1 activity was dependent on IL-2 concentration, and occured specfically in cytosolic fraction. Similar alteration was observed in IL-2 sensitive murine T-lymphoblasts. Neither activity of protein phophatase PP2A nor PP2C showed alteration during the IL-2 stimulation. These results suggest that PP1 plays an important role in early events of the intracellular growth signaling through the IL-2 receptor.

本研究测定了自身免疫易感型MRL/MpJ-1 pr/1 pr小鼠（MRL/1 pr小鼠）和两种对照品系MRL/MpJ-+/+小鼠（MRL/+/+小鼠）及C3 H/HeJ小鼠的T和B淋巴细胞中蛋白磷酸酶PP 1和PP 2 A的活性。在用Co^<2+>-胰蛋白酶处理淋巴细胞后测量的潜在PP 1活性在T淋巴细胞中比B淋巴细胞中高得多。然而，在MRL/1 pr小鼠和对照组之间没有观察到活性差异。正常小鼠T和B淋巴细胞的自发PP 2A活性水平相似，但MRL/1 pr小鼠T淋巴细胞的潜在PP 2A活性显著高于对照组。在IL-2依赖的小鼠细胞毒性T细胞系CTLL-2中，IL-2诱导Co^<2+>-胰蛋白酶处理的蛋白磷酸酶PP 1活性的快速和短暂降低。PP 1活性在45 min内下降到最低水平，为对照值的70%，其下降程度与IL-2浓度有关，且在胞浆中表现出特异性。在IL-2敏感的鼠T淋巴母细胞中观察到类似的改变。在IL-2刺激过程中，蛋白磷酸酶PP 2A和PP 2C的活性都没有改变。这些结果表明，PP 1通过IL-2受体在细胞内生长信号的早期事件中起重要作用。

项目成果

Kunimi Kikuchi: "Expressions and activities of protein phosphatases during carcinogenesis,regeneration,and cell cycle." Advances in Protein Phosphatases. 7. 221-236 (1993)

Kunimi Kikuchi：“蛋白磷酸酶在癌变、再生和细胞周期过程中的表达和活性。”

Koji Nakamura: "Cell cycle dependent gene expressions and activities of protein phosphatases PP1 and PP2A in mouse NIH3T3 fibroblasts." Biochemical and Biophysical Research Communications. 187. 507-514 (1992)

Koji Nakamura：“小鼠 NIH3T3 成纤维细胞中蛋白磷酸酶 PP1 和 PP2A 的细胞周期依赖性基因表达和活性。”

Nakamura, K., Koda, T., Kakunuma, M., Matsuzawa, S., Kitamura, K., Mizuno, Y., and Kikuchi, K.: "Cell cycle dependent gene expressions and activities of protein phosphatases PP1 and PP2A in mouse NIH3T3 fibroblasts." Biochemical and Biophysical Research C

Nakamura, K.、Koda, T.、Kakunuma, M.、Matsuzawa, S.、Kitamura, K.、Mizuno, Y. 和 Kikuchi, K.：“蛋白磷酸酶 PP1 和 PP2A 的细胞周期依赖性基因表达和活性

Kakinoki, Y., Kitamura, K., Matsuzawa, S., Mizuno, Y., Miyazaki, T., and Kikuchi, K.: "Gene expressions and activities of protein phophatases PP1 and PP2A in rat liver regeneration after partial hepatectomy." Biochemical and Biophysical Research Communica

Kakinoki, Y.、Kitamura, K.、Matsuzawa, S.、Mizuno, Y.、Miyazaki, T. 和 Kikuchi, K.：“部分肝切除术后大鼠肝脏再生中蛋白磷酸酶 PP1 和 PP2A 的基因表达和活性。

Mostafa Saasat: "Gene expression of protein phosphatases in rat ascites hepatoma cell lines." Cancer Detection and Prevention. 18(印刷中). (1994)

Mostafa Saasat：“大鼠腹水肝癌细胞系中蛋白质磷酸酶的基因表达。”18（出版中）。