PHOSPHORYLATION OF THE FUSED PROTEIN-KINASE IN RESPONSE TO SIGNALING FROM HEDGEHOG

The hedgehog gene (hh) of Drosophila melanogaster exerts both short- a nd long-range effects on cell patterning during development. The produ ct of hedgehog is a secreted protein that apparently acts by triggerin g an intracellular signaling pathway, but little is known about the de tails of that pathway. The Drosophila gene fused (fu) encodes a serine /threonine-protein kinase that genetic experiments have implicated in signaling initiated by hedgehog. Here we report that the fused protein is phosphorylated during the course of Drosophila embryogenesis, as a result of hedgehog activity. In cell culture, phosphorylation of fuse d protein occurs in response to the biologically active form of hedgeh og and cannot be blocked by activation of protein kinase A, which is t hought to be an antagonist of signaling from hedgehog. These results s uggest that fused and protein kinase A function downstream of hedgehog but in parallel pathways that eventually converge distal to fused. Th e reconstruction of signaling from hedgehog in cell culture should pro vide further access to the mechanisms by which hedgehog acts.