BIOCHEMICAL AND FUNCTIONAL-CHARACTERIZATION OF THE MURINE ROS PROTOONCOGENE

The ros gene was originally found because it can, when mutated, induce malignant transformation. The proto-oncogene encodes an orphan recept or tyrosine kinase. We report here the isolation and characterization of the mouse c-ros cDNA and, in addition, the biochemical characteriza tion of the receptor. Both, the endogenous c-ros protein from embryona l tissues and the recombinant protein are glycosylated molecules with an apparent molecular weight of 260 000. Pulse-chase analysis in Sf9 c ells demonstrates that the c-ros protein is synthesized as a single ch ain, uncleaved molecule. Since the specific ligand of c-ros is not kno wn, a hybrid receptor (trk/c-ros) which transmits c-ros-specific signa ls in response to nerve growth factor (NGF) was used to study the biol ogical activities. In NIH3T3 cells, this trk/c-ros hybrid induces grow th, a fusiform cell shape, and loss of contact inhibition of growth. H owever, the active hybrid receptor cannot replace IL-3 as survival fac tor in 32D myeloid cells. Compared to other receptors, the active c-ro s tyrosine kinase domain displays thus overlapping, but not identical signalling specificities.