PROTEOGLYCAN-MEDIATED SIGNALING IN CELL ADHESION

细胞粘附中蛋白聚糖介导的信号传导

• 批准号: 2022786
• 负责人: JOHN R. COUCHMAN
• 金额: $ 19万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-01-01 至 1997-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2022786
• 关键词: CHO cells; affinity chromatography; cell adhesion; cytoskeleton; fibronectins; gene mutation; immunofluorescence technique; integrins; intermolecular interaction; laboratory rabbit; ligands; molecular cloning; mucopolysaccharides; phosphorylation; protein kinase C; protein structure function; proteoglycan; receptor coupling; recombinant proteins; syndecan; synthetic peptide

Cellular interactions with extracellular matrix molecules are known to be involved in may developmental, repair, and homeostatic processes, but only recently has it been established that these interactions initiate transmembrane signalling events. The most well studied pathways to date involve tyrosine phosphorylations initiated by Beta1 and Beta3 integrin receptor-ligand interactions. the adhesion of most anchorage-dependent cells in culture, and some in vivo, is characterized by structures known as focal contacts or focal adhesions. These structures are thought to be integral to wound healing processes was well as providing stable anchorage for normal cells, but are often change in structure and composition in transformed cells, where they may even be absent. They are also an excellent model for transmembrane signalling. While many focal adhesion constituents are known, the process of assembly is not understood. Both tyrosine phosphorylation and subsequent protein kinase C (PKC) activity may be involved in their formation and in this respect, the pathways resemble those for some growth factor and lymphocyte receptor interactions. The long term goal of this research is to understand the molecular events leading to the formation and maintenance of focal adhesions in primary cultured cells. It is proposed that cells forming adhesions on a fibronectin substrate utilize a dual receptor system involving both integrins and cell surface proteoglycans. The latter may promote PKC activity and the assembly of focal adhesions. The transmembrane proteoglycan involved in this process has recently been identified as a member of the syndecan family of proteoglycans.

已知细胞与细胞外基质分子的相互作用 参与可能的发育、修复和稳态过程，但是 直到最近才确定这些相互作用引发了 跨膜信号传导事件。 迄今为止研究最深入的途径 涉及由 Beta1 和 Beta3 整合素引发的酪氨酸磷酸化 受体-配体相互作用。 大多数锚固依赖的附着力 培养中的细胞和一些体内的细胞具有已知的结构特征 作为焦点接触或焦点粘连。 这些结构被认为 成为伤口愈合过程不可或缺的一部分，并提供稳定的 正常细胞的锚定，但结构和结构经常发生变化 转化细胞中的成分，甚至可能不存在。 他们 也是跨膜信号传导的优秀模型。 虽然很多 粘着斑成分已知，但组装过程未知 明白了。 酪氨酸磷酸化和随后的蛋白激酶 C (PKC) 活动可能参与其形成，在这方面， 这些途径类似于某些生长因子和淋巴细胞的途径 受体相互作用。 这项研究的长期目标是 了解导致形成和维持的分子事件 原代培养细胞中的粘着斑。 建议细胞 利用双受体在纤连蛋白基质上形成粘附 涉及整合素和细胞表面蛋白聚糖的系统。 这 后者可能促进 PKC 活性和粘着斑的组装。 这 参与这一过程的跨膜蛋白多糖最近被 被鉴定为蛋白聚糖多聚糖家族的成员。