DROSOPHILA UNPAIRED ENCODES A SECRETED PROTEIN THAT ACTIVATES THE JAKSIGNALING PATHWAY

In vertebrates, many cytokines and growth factors have been identified as activators of the JAK/STAT signaling pathway. In Drosophila, TAK a nd STAT molecules have been isolated, but no ligands or receptors capa ble of activating the pathway have been described. We have characteriz ed the unpaired (upd) gene, which displays the same distinctive embryo nic mutant defects as mutations in the Drosophila TAK (hopscotch) and STAT (stat92E) genes. Upd is a secreted protein, associated with the e xtracellular matrix, that activates the TAK pathway. We propose that U pd is a ligand that relies on TAK signaling to stimulate transcription of pair-rule genes in a segmentally restricted manner in the early Dr osophila embryo.