THE NONRECEPTOR PROTEIN-TYROSINE-PHOSPHATASE CORKSCREW FUNCTIONS IN MULTIPLE RECEPTOR TYROSINE KINASE PATHWAYS IN DROSOPHILA

Corkscrew (csw) encodes a nonreceptor protein tyrosine phosphatase (PT Pase) that has been implicated in signaling from the Torso receptor ty rosine kinase (RTK). csw mutations, unlike for mutations, are associat ed with zygotic lethality, indicating that Csw plays additional roles during development. We have conducted a detailed phenotypic analysis o f csw mutations to identify these additional functions of Csw. Our res ults indicate that Csw operates positively downstream of other Drosoph ila RTKs such as the Drosophila epidermal growth factor receptor (DER) , the fibroblast growth factor receptor (Breathless), and likely other RTKs. This model is substantiated by specific dosage interactions bet ween csw and DER. It is proposed that Csw is part of the evolutionaril y conserved ''signaling cassette'' that operates downstream of all RTK s. In support of this hypothesis, we demonstrate that SHP-2, a vertebr ate PTPase similar to Csw and previously implicated in RTK signaling, encodes the functional vertebrate homologue of Csw. (C) 1996 Academic Press, Inc.