The long-term goal of this application is to understand the role played by phospholipase C-gamma (PLC-gamma) in regulating cell growth and differentiation. PLC-gamma is a key regulator of growth factor signaling pathways and is therefore a potential target for new drugs in the control of cancer. This application proposes to investigate PLC-gamma function by studying the homolog encoded by the Drosophila gene small wing (sl).
The specific aims of this proposal are to: 1) Characterize when and where SL is expressed. Recombinant GST-SL fusion proteins will be purified from E. coli and used to raise anti-SL monoclonal antibodies. The tissue distribution and timing of SL expression in the eye and wing imaginal discs will then be determined by immunohistochemistry with these antibodies in combination with confocal microscopy. 2) Conduct an in vivo structure/function analysis of SL. A construct containing the sl transcription unit will be modified in various ways in vitro and each modified form introduced into an sl null strain by germline transformation. The effect of each alteration on eye and wing phenotypes will be determined. 3) Identify other proteins participating in SL-mediated signaling. A DEB mutagenesis of an sl null strain will be used to look for sl modifiers. Mutations that affect sl eye or wing phenotypes will be mapped, the genes responsible identified and their role in SL-mediated signaling determined. 4) Investigate the role of SL in other signaling pathways. The sl mutant phenotypes in the embryo, larva and adult wing will be examined in more detail. Larval cuticle preparations will be examined and cell size, cell number and cell survival during development will be measured in sl homozygotes and various double mutants to determine whether SL is involved in other RTK signaling pathways.
| Mankidy, Rishikesh; Hastings, Jeremy; Thackeray, Justin R (2003) Distinct phospholipase C-gamma-dependent signaling pathways in the Drosophila eye and wing are revealed by a new small wing allele. Genetics 164:553-63 |
| Manning, Charlene M; Mathews, Wendy R; Fico, Leah P et al. (2003) Phospholipase C-gamma contains introns shared by src homology 2 domains in many unrelated proteins. Genetics 164:433-42 |
| Abbeyquaye, Tetteh; Riesgo-Escovar, Juan; Raabe, Thomas et al. (2003) Evolution of Gab family adaptor proteins. Gene 311:43-50 |
