THE HEAT-SHOCK-PROTEIN-83 (HSP83) IS REQUIRED FOR RAF-MEDIATED SIGNALING IN DROSOPHILA

The heat shock protein Hsp90 has been shown to associate with various cellular signalling proteins such as steroid hormone receptors, src-li ke kinases and the serine/threonine kinase Raf. While the interaction between steroid hormone receptors and Hsp90 appears to be essential fo r ligand binding and activation of the receptors, the role of Hsp90 in Raf activation is less clear. We have identified mutations in the hsp 83 gene, the Drosophila homologue of hsp90, in a search for dominant m utations that attenuate signalling from Raf in the developing eye. The mutations result in single amino acid substitutions in the Hsp83 prot ein and cause a dominant-negative effect on the function of the wild-t ype protein. We show that both wild-type and mutant forms of Hsp83 bin d to the activated Drosophila Raf but the mutant Hsp83 protein causes a reduction in the kinase activity of Raf. Our results indicate that H sp83 is essential for Raf function in vivo.