KSR, A NOVEL PROTEIN-KINASE REQUIRED FOR RAS SIGNAL-TRANSDUCTION

We have identified and characterized two genes in Drosophila whose pro ducts are required for activated RAS to signal with normal efficiency, but do not appear to effect signaling by activated RAF, One encodes t he beta subunit of type I geranylgeranyl transferase, a prenylation en zyme essential for targeting RAS to the plasma membrane, The other enc odes a protein kinase that we have named kinase suppressor of ras (ksr ). By genetic criteria, we show that KSR functions in multiple recepto r tyrosine kinase pathways. We have isolated mammalian homologs of KSR that, together with the Drosophila gene, define a novel class of kina ses. Our results suggest that KSR is a general and evolutionarily cons erved component of the RAS signaling pathway that acts between RAS and RAF.