Analysis of structure and activation of some receptor-type tyrosine kinase oncogenes.
We first describe the characterization of proto-oncogene of v-ros in chicken and human genomes. v-ros sequence of UR2 avian sarcoma virus carries a hydrophobic short stretch upstream of the kinase domain, suggesting that its proto-oncogene encodes for a receptor molecule. Using v-ros DNA as a probe we isolated chicken and human c-ros proto-oncogenes. These c-ros DNAs contained a tyrosine kinase domain, transmembrane domain and a part of an extracellular domain carrying an N glycosylation site which was not acquired by UR2 sarcoma virus. These results strongly suggest that proto-oncogene c-ros encodes for a receptor of cell growth or differentiation factor(s) and that the v-ros sequence is a truncated form of this receptor molecule. Structural alteration and overexpression under the control of viral promoter may be crucial for transforming activity of v-ros gene. We then report another example where a receptor-type oncogene is qualitatively and quantitatively activated. By screening with various onc probes we detected two human glioblastomas which have amplification of structurally altered c-erbB1 (epidermal growth factor (EGF) receptor) gene. c-erbB1 gene in these tumors bears a small deletion within the extracellular domain, and the gene product 140 kd protein shorter than the normal 170 kd EGF receptor was heavily phosphorylated on tyrosine residue even without ligand in in vitro phosphorylation reaction. Thus, these mutated EGF receptors seem to be fixed as a "switch-on" form in signal transduction for cell growth and might be involved in the transformation of glial cells.
Shibuya
M
M
Institute of Medical Science, University of Tokyo, Japan.
Matsushime
H
H
Yamazaki
H
H
Wang
L H
LH
Fukui
Y
Y
Ueyama
Y
Y
Tamaoki
N
N
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002645:Chickens; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009857:Oncogenes; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human; D020794:Receptor Protein-Tyrosine Kinases