ABELSON LEUKEMIA VIRUS TRANSFORMATION

Abelson鼠白血病病毒(AbMLV)是一种快速转化的逆转录病毒 它含有癌基因v-abl。这种或其他致癌基因的表达 ABL的各种形式诱导多种类型的细胞转化并刺激 其他人的成长和分化。此外，ABL表达可以 是致命的。所有这些影响都是由单一产品介导的，该产品在 抗体-MLV的病例称为Abelson蛋白。这个分子是一个成员 非受体蛋白酪氨酸激酶家族和蛋白酪氨酸 单抗-MLV对细胞的任何作用都需要有激酶活性 成长。尽管Abelson蛋白改变细胞的机制 生长当然涉及到细胞内酪氨酸的磷酸化 蛋白质，对实际涉及的途径知之甚少。这个 这里提出的实验从五个方面解决了这个问题。首先，我们将 使用基因工程和生物选择的病毒来理解 蛋白质的特定部分在细胞转化中的作用 淋巴样细胞在体内和体外均有致死反应。第二，我们 将继续努力隔离显性负面转化 变种人。第三，我们将使用在 研究的前两部分，以了解突变的方式 改变Abelson蛋白的功能。第四，我们将在最近的基础上 观察到转化需要有活性的Abelson蛋白 Pre-B细胞进入细胞周期的G1期。最后，我们会 用抗-MLV条件突变体转化的前B淋巴细胞治疗 理解转型与分化之间的关系 抗体-MLV系统。总之，这些实验将有助于确定 激活的ab/基因改变细胞生长和 差异化。

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.