AN SH3-SH2-SH3 PROTEIN IS REQUIRED FOR P21(RAS1) ACTIVATION AND BINDS TO SEVENLESS AND SOS PROTEINS INVITRO

Activation of the sevenless protein-tyrosine kinase is required for the proper specification of R7 photoreceptors in the Drosophila eye. The activation of a Ras protein, p21Ras1, is a crucial early event in the signaling pathway, and constitutive activation of p21Ras1 is sufficient to induce all of the effects of sevenless action. Here we report that another gene, E(sev)2B, required for proper signaling by sevenless encodes a protein of the structure SH3-SH2-SH3. We further provide evidence that the E(sev)2B protein is required for activation of p21Ras1 but not for any subsequent events, and that this protein can bind in vitro to sevenless and to Son of sevenless (Sos), a putative guanine nucleotide exchange factor for p21Ras1. These results suggest that the E(sev)2B protein may act to stimulate the ability of Sos to catalyze p21Ras1 activation by linking sevenless and Sos in a signaling complex. We have renamed the E(sev)2B locus downstream of receptor kinases (drk).