FGF SIGNALLING BY CELL SURFACE PROTEOGLYCANS

细胞表面蛋白聚糖的 FGF 信号传导

• 批准号: 2403010
• 负责人: MARK S FILLA
• 金额: $ 2.86万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-15 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2403010
• 关键词: biological signal transduction; crosslink; fibroblast growth factor; growth factor receptors; immunoprecipitation; mitogens; phospholipase C; proteoglycan; receptor binding; surface property; syndecan; tissue /cell culture; transfection

Fibroblast growth factors (FGFs) regulate a range of physiological and pathological processes. They promote growth and differentiation of cell types found in tissues derived from all three embryonic germ layers and mediate aspects of cell embryonic development (e.g., muscle and nerve development) angiogenesis. cell motility, and also function significantly in regulating development of various tumor types. FGFs elicit cellular responses by binding and activating cell surface FGF receptor tyrosine kinases (FGFRs 1-4). Specific signal transduction pathways are initiated upon receptor activation leading to a variety of cellular responses. Cell surface heparan sulfate proteoglycans (HSPGs facilitate FGF/FGFR interactions. Several classes of HSPG exist; two of these are the syndecans (Synds 1-4), integral membrane HSPGs, and lipid-linked HSPGs such as cerebroglycan (CBG). Both forms are the focus of the experiments proposed here. Both forms bind FGF, but the different means of anchoring to the cell surface suggest that different responses to FGFs are regulated by which form mediates FGF/FGFr interactions. The goal of this research is to clarify the role that HSPGs play in mediating FGF signaling by asking questions of a cell expressing a single HSPG along with a single FGF receptor type. The specific aims are 1) determine if soluble Synd1 or CBG differ in their ability to mediate FGF signaling in FGFR positive/HSPG negative cells; 2) determine if cell surface anchored Synd1 or CBG co- expressed with a single type of FGFR in a lymphoid cell line normally devoid of these molecules differ in their ability to promote FGF binding to and/or activation of the FGFR: 3) assess the effects of modulating cell surface levels of Synd1 or CBG in inhibiting FGF binding to and/or activation of the FGFR in FGF responsive cells and 4) examine the ability of Synd1 and CBG to mediate activation of different FGF/FGFR signal transduction pathways in FGF responsive cells.

成纤维细胞生长因子（FGF）调节一系列生理和 病理过程。它们促进细胞的生长和分化 从所有三个胚胎细菌层中得出的组织中发现的类型， 介导细胞胚胎发育的各个方面（例如肌肉和神经 发育）血管生成。细胞运动性，并且也显着起作用 在调节各种肿瘤类型的发展中。 FGF会引起细胞 通过结合和激活细胞表面FGF受体酪氨酸的反应 激酶（FGFR 1-4）。启动特定的信号转导途径 受体激活导致各种细胞反应。细胞 表面硫酸乙酰肝素蛋白聚糖（HSPGS促进FGF/FGFR 互动。存在几类HSPG；其中两个是 Syndecans（Synds 1-4），整体膜HSPG和脂质连接HSPGS 例如小脑（CBG）。两种形式都是实验的重点 在这里提议。两种形式结合FGF，但锚定的不同方法 细胞表面表明对FGF的不同反应受到调节 形式介导FGF/FGFR相互作用。这项研究的目的是 为了阐明HSPG通过询问介导FGF信号的作用 表达单个HSPG以及单个FGF的细胞的问题 受体类型。具体目的是1）确定可溶性synd1或cbg是 它们介导FGFR阳性/HSPG中FGF信号传导的能力有所不同 负细胞； 2）确定细胞表面锚定Synd1或CBG是否共同 通常在淋巴样细胞系中用单一类型的FGFR表示 没有这些分子在促进FGF结合的能力上有所不同 TO和/或FGFR的激活：3）评估调节细胞的影响 Synd1或CBG的表面水平在抑制FGF与和/或 FGF响应细胞中FGFR的激活，4）检查能力 Synd1和CBG的介导不同FGF/FGFR信号的激活 FGF响应细胞中的转导途径。