Hedgehog Elicits Signal Transduction by Means of a Large Complex Containing the Kinesin-Related Protein Costal2

The hedgehog gene of Drosophila melanogaster encodes a secreted protein (HH) that plays a vital role in cell fate and patterning. Here we describe a protein complex that mediates signal transduction from HH. The complex includes the products of at least three genes: fused (a protein-serine/threonine kinase), cubitus interruptus (a transcription factor), and costal2 (a kinesin-like protein). The complex binds with great affinity to microtubules in the absence of HH, but binding is reversed by HH. Mutations in the extracatalytic domain of FU abolish both the biological function of the protein and its association with COS2. We conclude that the complex may facilitate signaling from HH by governing access of the cubitus interruptus protein to the nucleus.