ANALYSIS OF SRC64 SIGNALING COMPONENTS DURING OOGENESIS

Src家族的激酶被认为是复杂细胞事件的调节者，包括细胞的增殖、分化、存活和形态发生。在乳腺癌、结肠癌、肺癌和髓系白血病中，可以观察到Src家族激酶的过度表达或不适当的激活，并与肿瘤的发生或进展有关。已有研究表明，在肌动蛋白细胞骨架的重组过程中，Src家族的蛋白激酶起着关键作用，而肌动蛋白细胞骨架的重组过程与肿瘤的进展密切相关。这一建议的目的是进一步了解Src介导的导致肌动蛋白细胞骨架重排和形态发生事件的信号转导途径。为了解决这个问题，将利用一种无偏见的遗传方法来鉴定和表征果蝇卵子发生中的Src通路信号成分。在这个系统中，Src家族激酶，src64，是调节富含肌动蛋白的结构所必需的，这种结构被称为环管，它是将营养从哺乳细胞转移到发育中的卵母细胞所必需的。这项建议的具体目的是：1)鉴定和克隆两种先前发现的Src64缺陷的增强子，它们与细胞膜上的环管连接；2)进行进一步的增强子和抑制子筛选，目的是鉴定src64信号通路的新成分。鉴定果蝇卵子发生过程中Src64信号通路的组成有助于全面理解Src家族在形态发生中的作用。

The Src family kinases are well recognized as regulators of complex cellular events, including cell proliferation, differentiation, survival and morphogenesis. Overexpression or inappropriate activation of Src family kinases is observed in human cancers of the breast, colon, lung, and in myeloid leukemias and has been implicated in tumorigenesis or tumor progression. It has been demonstrated that Src family kinases play a critical role in reorganization of the actin cytoskeleton, a process strongly implicated in cancer progression. The goal of this proposal is to further understand Src-mediated signal transduction pathways that lead to rearrangement of the actin cytoskeleton and morphogenetic events. To address this question, an unbiased, genetic approach will be utilized for the identification and characterization of Src pathway signaling components in Drosophila oogenesis. In this system, the Src family kinase, Src64, is required for regulation of actin-rich structures, called ring canals, which are required for transfer of nutrients from nurse cells to the developing oocyte. The Specific Aims of this proposal are 1) to characterize and clone two previously identified enhancers of Src64 defects in attachment of ring canals to nurse cell membranes and 2) to conduct further enhancer and suppressor screens with the goal of identifying new components of the Src64 signaling pathway. Identification of components of the Src64 signaling pathway in Drosophila oogenesis should contribute to the general understanding of Src family kinase function in morphogenetic events.