Takahashi M, Buma Y, Iwamoto T, Inaguma Y, Ikeda H, Hiai H.
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.
Amino Acid Sequence
Cell Membrane / enzymology
DNA, Neoplasm / genetics
Molecular Sequence Data
Protein-Tyrosine Kinases / genetics*
Proto-Oncogene Proteins / genetics*
Proto-Oncogene Proteins c-ret
RNA, Messenger / genetics
Receptor Protein-Tyrosine Kinases*
Tumor Cells, Cultured / enzymology
GENETICS & HEREDITY
BIOCHEMISTRY & MOLECULAR BIOLOGY
|pSV2 proto-ret (RDB01163)