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.

该提议的目的是检查整联蛋白在 Rous肉瘤病毒的过程诱导细胞转化。 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标之一 PP60V-SRC的活性。 位点特异性诱变将用于改变磷酸化的 酪氨酸并修改整合素β链的内部域 其中包括磷酸化的酪氨酸。 向量将用于 将雏鸡整合素的正常和突变的β亚基引入ROUS 转化的细胞，恢复细胞和正常细胞以获得效果 这些突变体关于PP60V-SRC诱导转化的能力的能力 表型。 整联蛋白的磷酸化状态将在细胞中检查 整联蛋白突变体，细胞的膜粘附斑块部分 由不同的癌基因转化，在正常生理期间 过程。 整联蛋白与细胞外基质的相互作用 将通过使用不同的底物来确定角色来操纵 在转化的表型中的这些联系中。