Cloning and expression of the ret proto-oncogene encoding a tyrosine kinase with two potential transmembrane domains.
The nucleotide sequence of the ret proto-oncogene has been determined from cDNA clones isolated from a cDNA library of a THP-1 human monocytic leukemia cell line. Analysis of this sequence indicates that it encodes a protein which is structurally related to transmembrane receptors with a cytoplasmic tyrosine kinase domain. Unlike most growth factor receptors, it contains two hydrophobic regions which are potential transmembrane domains. Comparison of the sequence of the ret proto-oncogene with that of the ret transforming gene revealed that, in addition to the amino-terminal truncation, the last 51 carboxy-terminal amino acids of the ret proto-oncogene were replaced with 9 unrelated amino acids of the ret transforming gene. The focus forming activity of the ret cDNA, containing both amino-terminal and caboxy-terminal truncations, was approximately 13-fold higher than that of cDNA containing only the amino-terminal truncation. This suggests a possible role for the carboxy-terminal sequence in activation of transforming potential of the ret proto-oncogene. When transcription of the ret proto-oncogene was examined in a variety of mouse tissues, we detected its transcription in normal mouse spinal cord and lymphadenopathy of C3H/HeJ-gld/gld and MRL/Mp-lpr/lpr mice.
Takahashi
M
M
Laboratory of Experimental Pathology, Aichi Cancer Center Research Institute, Japan.
Buma
Y
Y
Iwamoto
T
T
Inaguma
Y
Y
Ikeda
H
H
Hiai
H
H
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000235:genetics; D029721:Drosophila Proteins; D015870:Gene Expression; D015723:Gene Library; D006801:Humans; D008969:Molecular Sequence Data; D010957:Plasmids; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases; D015183:Restriction Mapping; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000201:enzymology
D004273:DNA, Neoplasm; D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila