Protein kinase C-mediated bidirectional regulation of endothelial cell growth

蛋白激酶 C 介导的内皮细胞生长双向调节

• 批准号: 05670039
• 负责人: TAKUWA Noriko
• 金额: $ 1.34万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670039/
• 关键词: Cell cycle; Protein kinase C; Cyclin-dependent kinase; Endothelial cell

In human umbilical vein endothelial cells, the protein kinase C (PKC) stimulation during the early G1 phase leads to potentiations in growth factor-stimulated DNA synthesis, the activation of cdc2 and cdk2 cyclin-dependent kinases, and the mRNA expression of cdc2, cyclins A,D1 and E,but not cdk2 or cdk4. Conversely, the PKC stimulation in the late G1 phase completely inhibits DNA synthesis, the activation of cyclin-dependent kinases, and the mRNA expression of the same set of molecules except cyclin D1. Further, we found that the PKC stimulation bimodally regulates the message levels of E2F1 and B-myb, which are transcription factors implicated in the control of the mammalian cell cycle progression. These results indicate that the PKC signal transduction pathway, depending on the timing of activation in the G1 phase, either positively or negatively regulates the message level of growth-regulating genes that are crucial for the G1 to S phase progression.

在人脐静脉内皮细胞中，早期 G1 期的蛋白激酶 C (PKC) 刺激会导致生长因子刺激的 DNA 合成增强、cdc2 和 cdk2 细胞周期蛋白依赖性激酶的激活以及 cdc2、细胞周期蛋白 A、D1 和 E 的 mRNA 表达，但不增强 cdk2 或 cdk4。相反，G1 晚期的 PKC 刺激完全抑制 DNA 合成、细胞周期蛋白依赖性激酶的激活以及除细胞周期蛋白 D1 之外的同一组分子的 mRNA 表达。此外，我们发现 PKC 刺激双峰调节 E2F1 和 B-myb 的信息水平，这些转录因子涉及哺乳动物细胞周期进程的控制。这些结果表明，根据 G1 期激活的时间，PKC 信号转导途径可以正向或负向调节对 G1 到 S 期进展至关重要的生长调节基因的信息水平。

项目成果

N.Takuwa, W.Zhou, and Y.Takuwa: "Calcium, calmodulin, and cell cycle progression." Cellular Signalling. (In press). (1995)

N.Takuwa、W.Zhou 和 Y.Takuwa：“钙、钙调蛋白和细胞周期进展。”

J. Abe, W. Zhou, J. Taguchi, N. Takuwa, K. Miki, H. Okazaki, K. Kurokawa, M. Kumada, and Y. Takuwa: "Suppression of neointiwal smooth muscle cell accumulation in viro by antisense cdo2 and cdk2 oligonucleotioles in rat carotia artery." Biochew. Biopys. Re

J. Abe、W. Zhou、J. Taguchi、N. Takuwa、K. Miki、H. Okazaki、K. Kurokawa、M. Kumada 和 Y. Takuwa：“反义 cdo2 在体外抑制新内膜平滑肌细胞积累

J. Abe, W. Zhou, N. Takuwa, J. Taguchi, K. Kurokawa, M. Kuwada, and Y. Takuwa: "A fiwagillin cerivative ang : ogenesis inhibitor, AGM-1470,inhibits activation of cyclin-dependent kinases and phospharylation of retiooblastana gone producut but net protein

J. Abe、W. Zhou、N. Takuwa、J. Taguchi、K. Kurokawa、M. Kuwada 和 Y. Takuwa：“一种 fiwagillin cerivative ang：卵发生抑制剂 AGM-1470，抑制细胞周期蛋白依赖性激酶的激活，并且

N.Takuwa,W.Zhou,M.Kumada,and Y.Takuwa: "Ca^<2+>-dependent stimulation of retinoblastoma gene product phosphorylation and p34^<cdc2>kinase activation inserum stimulated human fibroblasts." J.Biol.Chem.268. 138-145 (1993)

N.Takuwa、W.Zhou、M.Kumada 和 Y.Takuwa：“视网膜母细胞瘤基因产物磷酸化和 p34^<cdc2> 激酶激活的 Ca^2 依赖性刺激刺激了人成纤维细胞。”

J.Abe, W.Zhou, J.Taguchi, N.Takuwa, K,Miki, H.Okazaki, K.Kurokawa, M.Kumada, and Y.Takuwa: "Suppression of neointimal smooth muscle cell accumulation in vivo by antisense cdc2 and cdk2 oligonucleotides in rat carotid artery." Biochem.Biophys.Res.Commun.19

J.Abe、W.Zhou、J.Taguchi、N.Takuwa、K、Miki、H.Okazaki、K.Kurokawa、M.Kumada 和 Y.Takuwa：“反义 cdc2 对体内新生内膜平滑肌细胞积累的抑制