Role of β isoform of protein kinase C in hepatocyte growth factor-induced signal transduction in pigment cells

蛋白激酶Cβ亚型在肝细胞生长因子诱导的色素细胞信号转导中的作用

• 批准号: 15591177
• 负责人: OKA Masahiro
• 金额: $ 2.24万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591177/
• 关键词: hepatocyte growth factor; protein kinase C; malignant melanoma; phosphatidylinositol 3-kinase; phosphorylation; Gab1; 色素細胞; シグナル伝達; アデノウイルスベクター

The signaling pathway of hepatocyte growth factor (HGF) through its receptor-tyrosine kinase c-Met was examined in human normal melanocytes and malignant melanoma cell lines. HGF-induced c-Met activation was observed in both melanocytes and melanoma cells, whereas phosphatidylinositol 3-kinase (PI3K), a downstream target of c-Met, was not activated in the melanocytes but enhanced in the melanoma cells. Therefore, the role of Gab1, the scaffolding adapter protein that couples activated c-Met and PI3K, was analyzed in these cells. Gab1 in the melanocytes showed an electrophoretic mobility slower than that of the melanoma cells, and the mobility shifted to that of the melanoma cells after the treatment with alkaline phosphatase, indicating that Gab1 is highly phosphorylated on serine and threonine in the melanocytes. Introuction of protein kinase C (PKC) βII in the melanoma cells using adenovirus vector, that is expressed in the melanocytes but is absent in the melanoma cells, resulted in serine and threonine phosphorylation of Gab1. Furthermore, the introduction of PKCβII suppressed HGF-induced activation of Pl3K. These results indicate that the HGF signaling process from Gab1 to PI3K is negatively regulated by PKCβII.

在人类正常黑色素细胞和恶性黑色素瘤细胞系中检查了肝细胞生长因子 (HGF) 通过其受体酪氨酸激酶 c-Met 的信号通路。在黑色素细胞和黑色素瘤细胞中均观察到 HGF 诱导的 c-Met 激活，而 c-Met 下游靶标磷脂酰肌醇 3-激酶 (PI3K) 在黑色素细胞中未激活，但在黑色素瘤细胞中增强。因此，我们分析了 Gab1（偶联激活的 c-Met 和 PI3K 的支架接头蛋白）在这些细胞中的作用。黑色素细胞中Gab1的电泳迁移率比黑色素细胞慢，碱性磷酸酶处理后迁移率转向黑色素瘤细胞，表明黑色素细胞中Gab1的丝氨酸和苏氨酸高度磷酸化。使用在黑色素细胞中表达但在黑色素瘤细胞中不存在的腺病毒载体将蛋白激酶 C (PKC) βII 引入黑色素瘤细胞中，导致 Gab1 的丝氨酸和苏氨酸磷酸化。此外，PKCβII 的引入抑制了 HGF 诱导的 Pl3K 激活。这些结果表明，从 Gab1 到 PI3K 的 HGF 信号传导过程受到 PKCβII 的负调控。

项目成果

Differential response of primary and metastatic melanomas to neutrophils attracted by IL-8

• DOI: 10.1002/ijc.10775
• 发表时间: 2003-01-20
• 期刊: INTERNATIONAL JOURNAL OF CANCER
• 影响因子: 6.4
• 作者: Schaider, H;Oka, M;Herlyn, M
• 通讯作者: Herlyn, M

Reciprocal regulation of MelCAM and AKT in human melanoma

• DOI: 10.1038/sj.onc.1206819
• 发表时间: 2003-10-09
• 期刊: ONCOGENE
• 影响因子: 8
• 作者: Li, G;Kalabis, J;Herlyn, M
• 通讯作者: Herlyn, M

Protein kinase C α associates with phospholipase D1 and enhances basal phospholipase D activity in a protein phosphorylation-independent manner in human melanoma cells.

蛋白激酶 C α 与磷脂酶 D1 结合，并以不依赖于蛋白磷酸化的方式增强人黑色素瘤细胞中基础磷脂酶 D 的活性。

• 发表时间: 2003
• 期刊: J.Invest.Dermatol. 121(1)
• 作者: Oka;M.;Kageshita;T.;Ono;T.;Goto;A.;Kuroki;T;Ichihashi;M.
• 通讯作者: M.

Oka, M., Kageshita, T., Ono, T., Goto, A., Kuroki, T., Ichihashi, M.: "Protein Kinase C α Associates with Phospholipase D1 and Enhances Basal Phospholipase D Activity in a Protein Phosphorylation-Independent Manner in Human Melanoma Cells"J.Invest.Dermato

Oka, M.、Kageshita, T.、Ono, T.、Goto, A.、Kuroki, T.、Ichihashi, M.：“蛋白激酶 C α 与磷脂酶 D1 结合并增强蛋白磷酸化中的基础磷脂酶 D 活性 -人类黑色素瘤细胞的独立方式”J.Invest.Dermato

In vivo elimination of CD25+ regulatory T cells leads to tumor rejection of B16F10 melanoma, when combined with interleukin-12 gene transfer

• DOI: 10.1111/j.0906-6705.2004.00198.x
• 发表时间: 2004-10-01
• 期刊: EXPERIMENTAL DERMATOLOGY
• 影响因子: 3.6
• 作者: Nagai, H;Horikawa, T;Ichihashi, M
• 通讯作者: Ichihashi, M