Activation of the ret-II oncogene without a sequence encoding a transmembrane domain and transforming activity of two ret-II oncogene products differing in carboxy-termini due to alternative splicing.
We previously reported the cloning of a transforming gene, ret-II, which contains the proto-ret kinase domain. In the present study ret-II cDNAs were cloned from a transformant and analyzed. The restriction map and nucleotide sequence indicated that the sequence upstream of the proto-ret kinase domain was replaced by another sequence, which encoded a fusion protein composed of 899 amino acids. This non-proto-ret sequence differed from that of the ret previously reported and had no hydrophobic amino acid stretch for a transmembrane domain. Furthermore, we obtained two kinds of ret-II cDNAs differing in their 3' regions and found that the differences were generated by alternative splicing. From these cDNAs, two types of oncogene products differing in their carboxy-terminal amino acid residues were predicted. The two products exhibited similar transforming activity in NIH3T3 cells. These data indicate that activation of proto-ret can occur as a result of replacement of the extra-cellular and transmembrane domains with the hydrophilic sequence. In addition, differences in the carboxy-terminal amino acid residues in the two types of ret-II oncogene products have no influence on the transforming activity of the ret-II oncogene.
Ishizaka
Y
Y
Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan.
Ochiai
M
M
Tahira
T
T
Sugimura
T
T
Nagao
M
M
D000595:Amino Acid Sequence; D001324:Autoantigens; D001483:Base Sequence; D015152:Blotting, Northern; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D004247:DNA; D000077614:Golgi Matrix Proteins; D006801:Humans; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000502:physiology; D009857:Oncogenes; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing; D015183:Restriction Mapping; D033921:Vesicular Transport Proteins
D001324:Autoantigens; C060042:GOLGA5 protein, human; D000077614:Golgi Matrix Proteins; D008565:Membrane Proteins; D015345:Oligonucleotide Probes; D009856:Oncogene Proteins, Viral; D011498:Protein Precursors; D033921:Vesicular Transport Proteins; D004247:DNA; D011494:Protein Kinases