A second example illustrating the utility of Drosophila for investigating toxin activities in vivo is provided by studies of Helicobacter pylori (Fig. 2C) , which is associated with the development of gastric ulcers and cancer in humans. Under normal circumstances, ligand-initiated receptor tyrosine kinase (RTK) signaling in both fly and mammalian cells is mediated by a receptorassociated protein complex including Grb2 (Drk), Gab (Dos) and Shp-2 [Corkscrew (Csw)] (Drosophila protein names are shown in parentheses) that then activates signaling via the downstream components of the Ras-MAPK pathway. Drosophila played a prominent role in discovering key components of this pathway and in establishing the order of molecular events that take place during signaling (Simon, 2000) . In mammalian cells, the H. pylori virulence factor CagA activates RTK signaling at the level of SHP-2, a tyrosine phosphatase that is homologous to Drosophila Csw (Hatakeyama, 2008; Hatakeyama, 2009) , which acts downstream of Gab (Dos in flies) (Herbst et al., 1996; Raabe et al., 1996) . Studies in Drosophila confirmed the hypothesis that CagA can bypass the need for signaldependent activation of Dos in an intact organism, because CagA expression in Drosophila embryos or in the adult eye was capable of rescuing dos-mutant phenotypes (Botham et al., 2008) . Furthermore, the ability to activate effectors of the Sevenless RTK pathway in the eye was shown to be dependent on the downstream effector Csw, validating the hypothesized role of CagA in the RTK signaling pathway acting between Gab (Dos) and SHP-2 (Csw).