VEIN IS A NOVEL COMPONENT IN THE DROSOPHILA EPIDERMAL GROWTH-FACTOR RECEPTOR PATHWAY WITH SIMILARITY TO THE NEUREGULINS

The activation signal from tyrosine kinase receptors, such as the epid ermal growth factor receptor (EGFR), is relayed via a highly conserved intracellular pathway involving Ras, Raf, and MAPK. In Drosophila, th e EGFR and components of the intracellular pathway are broadly express ed, yet receptor activation evokes tissue-specific cell responses. Ext racellular events that lead to receptor activation are one mechanism b y which signaling is modulated. Here we show molecular and genetic evi dence that Drosophila vein (vn) encodes a candidate EGFR ligand and th at vn expression is spatially restricted. Consequently, vn may promote tissue-specific receptor activation. Unlike two other ligands, Gurken (Grk) and Spitz (Spi), which are transforming growth factor alpha-lik e proteins, Vn has both an immunoglobulin-like and an EGF-like domain. This combination of domains mirrors those in the vertebrate neureguli ns that bind EGFR relatives.