DISABLED IS A PUTATIVE ADAPTER PROTEIN THAT FUNCTIONS DURING SIGNALING BY THE SEVENLESS RECEPTOR TYROSINE KINASE

DRK, the Drosophila homolog of the SH2-SH3 domain adaptor protein Grb2 , is required during signaling by the sevenless receptor tyrosine kina se (SEV). One role of DRK is to provide a link between activated SEV a nd the Ras1 activator SOS. We have investigated the possibility that D RK performs other functions by identifying additional DRK-binding prot eins. We show that the phosphotyrosine-binding (PTB) domain containing protein Disabled (DAB) binds to the DRK SH3 domains. DAB is expressed in the ommatidial clusters, and loss of DAB function disrupts ommatid ial development. Moreover, reduction of DAB function attenuates signal ing by a constitutively activated SEV. Our biochemical analysis sugges ts that DAB binds SEV directly via its PTB domain, becomes tyrosine ph osphorylated upon SEV activation, and then serves as an adaptor protei n for SH2 domain-containing proteins. Taken together, these results in dicate that DAB is a novel component of the SEV signaling pathway.