DAUGHTER OF SEVENLESS IS A SUBSTRATE OF THE PHOSPHOTYROSINE PHOSPHATASE CORKSCREW AND FUNCTIONS DURING SEVENLESS SIGNALING

The SH2 domain-containing phosphotyrosine phosphatase Corkscrew (CSW) is an essential component of the signaling pathway initiated by the ac tivation of the sevenless receptor. tyrosine kinase (SEV) during Droso phila eye development We have used genetic and biochemical approaches to identify a substrate for CSW. Expression of a catalytically inactiv e CSW was used to trap CSW in a complex with a 115 kDa tyrosine-phosph orylated substrate. This substrate was purified and identified as the product of the daughter of sevenless (dos) gene. Mutations of dos were identified in a screen for dominant mutations which enhance the pheno type caused by overexpression of inactive CSW during photoreceptor dev elopment. Analysis of dos mutations indicates that DOS is a positive c omponent of the SEV signaling pathway and suggests that DOS dephosphor ylation by CSW may be a key event during signaling by SEV.