Biochemical and functional characterization of the murine ros protooncogene.
The ros gene was originally found because it can, when mutated, induce malignant transformation. The protooncogene encodes an orphan receptor tyrosine kinase. We report here the isolation and characterization of the mouse c-ros cDNA and, in addition, the biochemical characterization of the receptor. Both, the endogenous c-ros protein from embryonal tissues and the recombinant protein are glycosylated molecules with an apparent molecular weight of 260,000. Pulse-chase analysis in Sf9 cells demonstrates that the c-ros protein is synthesized as a single chain, uncleaved molecule. Since the specific ligand of c-ros is not known, a hybrid receptor (trk/c-ros) which transmits c-ros-specific signals in response to nerve growth factor (NGF) was used to study the biological activities. In NIH3T3 cells, this trk/c-ros hybrid induces growth, a fusiform cell shape, and loss of contact inhibition of growth. However, the active hybrid receptor cannot replace IL-3 as survival factor in 32D myeloid cells. Compared to other receptors, the active c-ros tyrosine kinase domain displays thus overlapping, but not identical signalling specificities.
Max-Delbrück-Laboratorium in der Max-Planck-Gesellschaft, Köln, Germany.
D
D
Riethmacher
O
O
Langholz
S
S
Gödecke
M
M
Sachs
C
C
Birchmeier
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D002478:Cells, Cultured; D051379:Mice; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D015398:Signal Transduction; D018411:Spodoptera
D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; C483813:Ros1 protein, mouse