INTERACTION OF ONCOGENES WITH AVIAN ERYTHROID CELLS

在动物的整个生命中，造血系统的作用是 产生髓系、红系和淋巴系的成熟细胞。 这个系统由细胞表面相互作用的复杂网络控制 涉及细胞-细胞和细胞-生长因子系统。白血病可以是 被视为这些监管互动中的一种崩溃。我们的目标是 找出这些重要的相互作用，控制着增长和 造血细胞的分化，以确定其机制 急性白血病是否能提供一种独特的系统来研究 这个网络可能被扰乱的机制。禽类逆转录病毒 是一个特别吸引人的模型系统 它们提供了一个系统，在这个系统中，造血细胞可以在 在体外，癌基因产物是膜糖蛋白，温度 有敏感的突变体可以使癌基因 已停用。因此，有可能研究相互作用。 病毒癌基因与细胞的关系，并确定其生长机制 的细胞可能会受到干扰；此外，遵循热 癌基因的失活，正常的细胞调节分子 在控制随后的分化过程中发挥着重要作用 可以辨认出来。在这项建议中，我们的具体目标是： 1.为鉴定禽红母细胞增多症病毒s13的致癌基因。 通过分子克隆前病毒并鉴定癌基因产物 负责细胞转化； 2.利用S13和禽红母细胞病现有的温度突变株 病毒株ES4研究这些癌基因的相互作用 两种带有红系细胞的病毒；以及 3.使用温度敏感的s13和aev转化的红细胞。 与抗红系表面抗原的单抗一起 确定正常的细胞表面受体在 红系细胞的分化，尤其是鸡转铁蛋白 受体。

The hematopoietic system functions throughout the life of an animal to produce the mature cells of the myeloid, erythroid and lymphoid lineages. This system is controlled by a complex network of cell surface interactions involving both cell-cell and cell-growth factor systems. Leukemia can be viewed as a breakdown in these regulatory interactions. Our objectives are to identify these important interactions which control the growth and differentiation of hematopoietic cells in order to identify mechanisms that could acute leukemia provide a unique system to investigate possible mechanisms by which this network can be perturbed. The avian retroviruses that cause erythroblastosis are a particularly attractive model system in that they provide a system where hematopoietic cells can be transformed in vitro, the oncogene products are membrane glycoproteins, and temperature sensitive mutants are available which allow the oncogene to be inactivated. Therefore it is possible to study the interaction of the viral oncogene with the cell and to identify mechanisms by which the growth of of the cells can be perturbed; in addition, following thermal inactivation of the oncogene, normal cellular regulatory molecules which are playing important roles in controlling the subsequent differentiation can be identified. In this proposal our specific aims are: 1. to characterize, the oncogene of the avian erythroblastosis virus S13 by molecularly cloning the provirus and identifying the oncogene product responsible for cell transformation; 2. to use existing temperature mutants of S13 and avian erythroblastosis virus strain ES4 to investigate the interaction of the oncogenes of these two viruses with erythroid cells; and 3. to use the temperature sensitive S13 and AEV transformed erythroblasts together with monoclonal antibodies against erythroid surface antigens to identify normal cell surface receptors that play a role in the differentiation of erythroid cells, in particular the chicken transferrin receptor.