ANALYSIS OF SRC64 SIGNALING COMPONENTS DURING OOGENESIS

Src家族激酶被认为是复杂细胞事件的调节剂，包括细胞增殖、分化、存活和形态发生。Src家族激酶的过度表达或不适当激活在人类乳腺癌、结肠癌、肺癌和髓性白血病中被观察到，并与肿瘤发生或肿瘤进展有关。已经证明Src家族激酶在肌动蛋白细胞骨架的重组中起关键作用，这一过程与癌症进展密切相关。本研究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，我们将采用一种无偏倚的遗传方法来鉴定和表征果蝇卵发生过程中Src通路信号传导成分。在这个系统中，Src家族激酶Src64是调节肌动蛋白丰富结构（称为环管）所必需的，环管是将营养物质从哺乳细胞转移到发育中的卵母细胞所必需的。本提案的具体目的是：1)表征和克隆两个先前鉴定的Src64环管附着于护理细胞膜缺陷的增强子；2)进行进一步的增强子和抑制子筛选，目的是鉴定Src64信号通路的新组分。确定果蝇卵发生过程中Src64信号通路的组成部分，有助于对Src家族激酶在形态发生事件中的功能有更全面的了解。

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.