ROLE OF INTEGRIN IN VIRAL TRANSFORMATION

整合素在病毒转化中的作用

• 批准号: 3194180
• 负责人: DAVID E BOETTIGER
• 金额: $ 20.05万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-05-01 至 1994-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3194180
• 关键词: Rous sarcoma virus; cell adhesion; cell differentiation; cell membrane; chick embryo; extracellular matrix; glycoproteins; linkage mapping; membrane proteins; molecular oncology; mutant; myogenesis; oncogenes; phosphorylation; protein tyrosine kinase; quail; site directed mutagenesis; transfection; transposon /insertion element; viral carcinogenesis

The objective of this proposal is to examine the role of integrin in the process of Rous sarcoma virus induced cell transformation. Integrin is a cellular receptor for fibronectin and other extracellular matrix components and is one of the putative targets for the tyrosine kinase activity of pp60v-src. Site specific mutagenesis will be used to change the phosphorylated tyrosine and to modify the internal domain of the beta chain of integrin which includes the phosphorylated tyrosine. Vectors will be used to introduce normal and mutated beta subunit of chick integrin into Rous transformed cells, revertant cells and normal cells to access the effect of these mutants on the ability of pp60v-src to induce a transformed phenotype. The state of phosphorylation of integrin will be examined in cell membrane adhesion plaque fractions for the integrin mutants, cells transformed by different oncogenes, and during normal physiological processes. The interaction of integrin with the extracellular matrix will be manipulated by use of different substrates to determine the role of these linkages in the transformed phenotype.

该提案的目的是研究整合素在 劳斯肉瘤病毒诱导细胞转化的过程。 整合素是一个 纤连蛋白和其他细胞外基质的细胞受体 成分，是酪氨酸激酶的假定靶点之一 pp60v-src 的活动。 位点特异性诱变将用于改变磷酸化 酪氨酸并修饰整合素β链的内部结构域 其中包括磷酸化的酪氨酸。 向量将用于 将鸡整合素的正常和突变 β 亚基引入 Rous 转化细胞、回复细胞和正常细胞均可获得效果 这些突变体对 pp60v-src 诱导转化能力的影响 表型。 将在细胞中检查整合素的磷酸化状态 整合素突变体、细胞的膜粘附斑块分数 由不同的癌基因转化，并在正常生理过程中 流程。 整合素与细胞外基质的相互作用 将通过使用不同的底物来操纵以确定作用 转化表型中的这些联系。