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.
