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.

研究了肝细胞生长因子(HGF)通过其受体酪氨酸激酶c-Met在人正常黑素细胞和恶性黑色素瘤细胞系中的信号转导途径。HGF诱导的c-Met在黑素细胞和黑色素瘤细胞中均被激活，而c-Met下游靶点磷脂酰肌醇3-激酶(PI3K)在黑素细胞中不被激活，但在黑色素瘤细胞中增强。因此，分析了GAB1在这些细胞中的作用，GAB1是连接活化的c-Met和PI3K的支架适配蛋白。黑素细胞GAB1的凝胶迁移率低于黑色素瘤细胞，经碱性磷酸酶处理后，GAB1向黑色素瘤细胞迁移，表明GAB1在黑素细胞的丝氨酸和苏氨酸上高度磷酸化。用腺病毒载体将在黑色素瘤细胞中表达但在黑色素瘤细胞中不表达的蛋白激酶CβII基因导入黑色素瘤细胞，使其丝氨酸和苏氨酸磷酸化。此外，PKCβII的引入抑制了肝细胞生长因子对Pl3K的激活。这些结果表明，从GAB1到PI3K的肝细胞生长因子信号转导过程受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