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Evolutionarily conserved developmental pathways


Cell survival: Epidermal growth factor and its receptor- the Ras pathway - ETS transcription factors

The Epidermal growth factor pathwayis conserved across numerous and diverse species, from nematodes to humans. In Drosophila, EGF-R responds to theligands Spitz and Argos. Whereas Spitz functions to enhance cell survival, Argos, an antagonist of EGF-R signaling, functions is a negative regulator of cell survival (Stemerdink, 1997). EGF-R targets ETS transcription factors during the inductionof neural tissue promoting cell surivival. EGF-R signals throughthe Ras pathway, a highly conservedsignal transduction pathway. MAPK (Rolled) is a component of the Ras pathway, is required at least three times in development: for the terminal system mediating responses to the Torso receptor, for neurogenic and wing vein pathways mediating responses to the EGF-receptor, and for the differentiation of photoreceptors, mediating responses to the Sevenless receptor. There is evidence that the interactionof ETS transcription factors with Serumresponse factor is also evolutionarily conserved. Human ETS transcription factors target cdc2,cyclinD1, c-fos, junB and prolactin. The Ras pathway functions to promote cell survival in radiation therapy (Pirollo, 1997), and genetic changes that constitutively activate intracellular survival pathways often occur in cancer (Eastman, 1995).


Drosophila                   Homologs in other species ----------                   ----------------------------Argos                        Other species: Epidermal growth factorSpitz                        C. elegans: Lin-3                             Mammalian: TGF-alpha, Epidermal growth factorEpidermal growth factor      C. elegans: Let-23 receptor                     Other species: Epidermal growth factor receptorRas Pathway components       Other species: Ras pathway componentsPointed                      C. elegans: Lin-1                             Mammalian: Ets-1 and Ets-2Yan                          C. elegans: Lin-1                             Mammalian: Ets-1 and Ets-2

References

Eastman, A. (1995). Survival factors, intracellular signal transduction, and theactivation of endonucleases in apoptosis. Semin. Cancer Biol. 6(1):45-52.

Pirollo, K. F., Hao, Z., Rait, A,, Ho, C. W. and Chang, E. H. (1997). Evidence supporting a signal transduction pathwayleading to the radiation-resistant phenotype in humantumor cells. Biochem. Biophys. Res. Commun. 230(1): 196-201. PubMed Citation: 9020045

Stemerdink, C. and Jacobs, J. R. (1997). Argos and Spitz group genes function to regulate midlineglial cell number in Drosophila embryos. Development 124(19): 3787-3796. PubMed Citation: 9367434



date revised: 15 Nov 97

Developmental Pathways conserved in Evolution

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