GENETIC ANALYSIS OF DROSOPHILA ABELSON TYROSINE KINASE

果蝇Abelson酪氨酸激酶的遗传分析

• 批准号: 3193775
• 负责人: F. Michael Hoffmann
• 金额: $ 18.48万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-06-01 至 1994-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3193775
• 关键词: Abelson leukemia virus; Drosophilidae; cell differentiation; cell growth regulation; chickens; cytogenetics; developmental genetics; gene expression; gene interaction; gene mutation; genetic manipulation; genetic mapping; genetic regulation; genetic regulatory element; genetic transcription; growth /development; molecular cloning; molecular genetics; nucleic acid hybridization; nucleic acid probes; oncoproteins; protein tyrosine kinase; protooncogene; virus protein

Tyrosine kinases are important regulatory molecules in the regulation of normal growth and differentiation and in the induction of aberrant growth properties by tyrosine kinase oncogenes. The goal of this proposal is to define how one particular tyrosine kinase, the Abelson proto-oncogene homolog of Drosophila, is regulated and to define the substrate macromolecules through which the tyrosine kinase activity modulates events in the cell. The advantage of studying the Abelson tyrosine kinase either as regulators or as substrates, or as other components in a regulatory pathway that functions during the normal growth and development of the organism. The pathway on which the Drosophila Abelson tyrosine kinase functions is required for the proper terminal differentiation and/or patterning of phenotypes caused by lesions in the Drosophila genes by suppression of specific lesions introduced into the kinase interacts with other proteins (e.g., regulatory factors and substrates) in mammalian cells should be suggested by our work in Drosophila. Eventually mammalian DNAs encoding regulatory proteins or substrates for a mammalian Abelson tyrosine kinase might be isolated directly by DNA hybridization under low stringency conditions using as probes DNA from the Drosophila genes identified in our studies. This information may be useful in understanding molecular mechanisms of transformation in that the Abelson tyrosine kinase is the activated oncoprotein both in mouse pre-B cell leukemias induced by Abelson murine leukemia virus and in some human leukemias including chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL). Identification of the genes that genetically interact with the Abelson product will provide the first clues to the biochemical processes that are modulated by the Abelson tyrosine kinase.

酪氨酸激酶是调节中重要的调节分子 正常的生长和分化以及异常生长的诱导 酪氨酸激酶癌基因的性质。 该提议的目的是 定义一种特定的酪氨酸激酶，阿伯森原始癌基因 果蝇的同源物受到调节并定义底物 酪氨酸激酶活性调节的大分子 单元中的事件。 研究阿伯森酪氨酸的优势 激酶作为调节剂或底物，或作为其他成分 调节途径在正常生长期间起作用 生物体的发展。 果蝇阿伯森的途径 适当的终端需要酪氨酸激酶功能 由病变引起的表型的分化和/或模式 果蝇基因是通过抑制引入的特定病变的 激酶与其他蛋白质相互作用（例如，调节因素和 我们在哺乳动物细胞中的底物应通过我们的工作建议 果蝇。 最终编码调节蛋白的哺乳动物DNA或 可以隔离哺乳动物阿伯森酪氨酸激酶的底物 直接在低严格条件下使用AS的DNA杂交 从我们的研究中鉴定出的果蝇基因的探针DNA。 这 信息可能有助于理解分子机制 转化是阿伯森酪氨酸激酶是激活的 小鼠前B细胞白血病中的癌蛋白均由阿伯森鼠诱导 白血病病毒和一些人类白血病（包括慢性骨髓） 白血病（CML）和急性淋巴细胞性白血病（全部）。 识别 遗传相互作用的基因将提供 生化过程的第一个线索是由 阿伯森酪氨酸激酶。