ABELSON LEUKEMIA VIRUS TRANSFORMATION

艾贝尔森白血病病毒转化

• 批准号: 2087231
• 负责人: NAOMI ROSENBERG
• 金额: $ 19.08万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-09-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2087231
• 关键词: 3T3 cells; Abelson leukemia virus; Retroviridae; Retroviridae disease; cell cycle; cell differentiation; cell growth regulation; cell type; clone cells; disease /disorder model; flow cytometry; gel electrophoresis; gene expression; genetic manipulation; genetic mapping; hematopoietic stem cells; host organism interaction; immunofluorescence technique; laboratory mouse; laboratory rabbit; leukocyte activation /transformation; membrane proteins; monoclonal antibody; murine leukemia virus; mutant; nucleic acid probes; oncogenic virus; phase contrast microscopy; protein sequence; protein structure function; protein tyrosine kinase; transforming virus; viral leukemogenesis; virus cytopathogenic effect; virus genetics; virus protein; virus replication

Abelson murine leukemia virus (Ab-MLV) is a rapidly transforming retrovirus that contains the oncogene v-abl. Expression of this or other oncogenic forms of abl induces transformation of many types cells and stimulates the growth and differentiation of others. In addition, expression of abl can be lethal. All of these effects are mediated by a single product, which in the case of Ab-MLV, is called Abelson protein. This molecule is a member of the non-receptor protein tyrosine kinase family and the protein tyrosine kinase activity is required for any of the effects of Ab-MLV on cell growth. Although the mechanism by which Abelson protein alters cellular growth most certainly involves tyrosine phosphorylation of cellular proteins, very little is known about the actual pathways involved. The experiments proposed here address this issue in five ways. First, we will use genetically engineered and biologically selected viruses to understand the role of particular portions of the protein in the transformation of lymphoid cells in vivo and in vitro and in the lethal response. Second, we will continue our efforts to isolate dominant negative transformation mutants. Third, we will use the most informative mutants identified in the first two parts of the study to understand the way in which the mutations alter Abelson protein function. Fourth, we will build on our recent observation that an active Abelson protein is required for transformed pre-B cells to transit the G1 phase of the cell cycle. Finally, we will use pre-B lymphocytes transformed by conditional mutants of Ab-MLV to understand the relationship between transformation and differentiation in the Ab-MLV system. Together these experiments will help determine the mechanism by which activated ab/ genes alter cellular growth and differentiation.

Abelson鼠白血病病毒（Ab-MLV）是一种快速转化的逆转录病毒 含有致癌基因v-abl的基因。这种或其他致癌基因的表达 各种形式的ABL诱导多种类型细胞的转化，并刺激 其他人的成长和分化。 此外，ABL的表达可 是致命的 所有这些作用都是由一种单一的产品介导的， Ab-MLV的情况称为Abelson蛋白。 这个分子是 非受体蛋白酪氨酸激酶家族和蛋白酪氨酸 激酶活性是Ab-MLV对细胞的任何作用所必需的 增长 尽管Abelson蛋白改变细胞的机制 生长最肯定涉及细胞的酪氨酸磷酸化， 蛋白质，很少有人知道有关的实际途径。 的 这里提出的实验以五种方式解决这个问题。 一是 使用基因工程和生物选择的病毒来了解 蛋白质的特定部分在转化中的作用 淋巴样细胞在体内和体外以及在致死反应中。 二是 我们将继续努力， 变种人 第三，我们将使用最丰富的突变体中确定的 研究的前两部分是为了了解突变的方式， 改变Abelson蛋白功能。 第四，我们将在近期 观察到转化需要活性Abelson蛋白， 前B细胞通过细胞周期的G1期。 最后我们将 使用Ab-MLV条件突变体转化的前B淋巴细胞， 理解转型与分化的关系， Ab-MLV系统。 这些实验将有助于确定 激活的ab/基因改变细胞生长的机制， 分化