CHARACTERIZATION OF FIBROBLAST GROWTH FACTOR RECEPTOR SIGNALING PATHWAYS

成纤维细胞生长因子受体信号通路的表征

• 批准号: 3874768
• 负责人: S A AARONSON
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3874768
• 关键词: biological signal transduction; enzyme substrate; epidermal growth factor; growth factor receptors; guanosinetriphosphatases; human tissue; keratinocyte; phospholipase C; protein tyrosine kinase; proteins; receptor binding; tissue /cell culture

Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor (FGF) family which acts on a variety of epithelial cell types, but is distinct from other known FGFs in that it is not mitogenic for fibroblasts or endothelial cells. We have found specific KGF binding to surface receptors on BALB/MK keratinocytes which was competed efficiently by acidic FGF, but with 100-fold lower efficiency by basic FGF. The pattern of binding and competition on BALB/MK and NIH/3T3 fibroblasts suggests that these cell types possess related but distinct FGF receptors. Scatchard analysis of KGF binding suggested two high affinity components and a third, high capacity/low affinity heparin-like component. Covalent affinity cross-linking of KGF to its receptor on BALB/MK cells also revealed two high affinity species. We have preliminarily characterized several early substrates of growth factor receptor tyrosine kinases. Some appear to be common to several different receptor pathways, e.g. , phospholipase C gamma (PLC-gamma) ; while others, such as the GTPase activating protein (GAP) of p2l ras, appear to be cell type- and/or ligand-specific. Both of these substrates directly link growth factor receptor signalling at the cell surface to diverse growth-related intracellular biochemical pathways. We have also identified a tyrosine-specific protein phosphatase from bovine liver, and characterized its activity on activated epidermal growth factor (EGF) receptor. The potential interaction of this phosphatase with FGF receptors is currently under investigation.

角质形成细胞生长因子（KGF）是成纤维细胞生长的成员 因子（FGF）家族，作用于多种上皮细胞类型，但是 与其他已知的 FGF 不同，它不具有促有丝分裂作用 成纤维细胞或内皮细胞。我们发现 KGF 与 BALB/MK 角质形成细胞上的表面受体有效竞争 酸性 FGF 的效率较低，但碱性 FGF 的效率低 100 倍。图案 BALB/MK 和 NIH/3T3 成纤维细胞的结合和竞争表明 这些细胞类型具有相关但不同的 FGF 受体。斯卡查德 KGF 结合分析表明有两种高亲和力成分和第三种， 高容量/低亲和力肝素样成分。共价亲和力 KGF 与其 BALB/MK 细胞上的受体的交联还揭示了两个 高亲和力物种。 我们已经初步表征了几种早期生长基质 因子受体酪氨酸激酶。有些似乎是几个人共有的 不同的受体途径，例如, 磷脂酶 C γ (PLC-γ) ; 而其他的，例如 p2l ras 的 GTP 酶激活蛋白 (GAP)， 似乎是细胞类型和/或配体特异性的。这两种基材 细胞表面的生长因子受体信号直接与 多种与生长相关的细胞内生化途径。我们还有 从牛肝中鉴定出一种酪氨酸特异性蛋白磷酸酶，并且 表征其对活化表皮生长因子 (EGF) 的活性 受体。该磷酸酶与 FGF 受体的潜在相互作用 目前正在接受调查。