DOS, A NOVEL PLECKSTRIN HOMOLOGY DOMAIN-CONTAINING PROTEIN REQUIRED FOR SIGNAL-TRANSDUCTION BETWEEN SEVENLESS AND RAS1 IN DROSOPHILA

The specification of the R7 photoreceptor cell in the developing eye o f Drosophila is dependent upon activation of the Sevenless (SEV) recep tor tyrosine kinase. By screening for mutations that suppress signalin g via a constitutively activated SEV protein, we have identified a nov el gene, daughter of sevenless (dos). DOS is required not only for sig nal transduction via SEV but also in other receptor tyrosine kinase si gnaling pathways throughout development. The presence of an amino-term inally located pleckstrin homology domain and many potential tyrosine phosphorylation sites suggests that DOS functions as an adaptor protei n able to interact with multiple signaling molecules. Our genetic anal ysis demonstrates that DOS functions upstream of Ras1 and defines a si gnaling pathway that is independent of direct binding of the DRK SH2/S H3 adaptor protein to the SEV receptor tyrosine kinase.