Cloning and expression of the ret proto-oncogene encoding a tyrosine kinase with two potential transmembrane domains

Oncogene. 1988 Nov;3(5):571-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Blotting, Northern
  • Cell Line
  • Cell Membrane / enzymology
  • Cloning, Molecular
  • DNA, Neoplasm / genetics
  • Drosophila Proteins*
  • Gene Expression
  • Gene Library
  • Humans
  • Molecular Sequence Data
  • Plasmids
  • Protein Conformation
  • Protein-Tyrosine Kinases / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-ret
  • Proto-Oncogenes*
  • RNA, Messenger / genetics
  • Receptor Protein-Tyrosine Kinases*
  • Restriction Mapping
  • Transcription, Genetic
  • Tumor Cells, Cultured / enzymology

Substances

  • DNA, Neoplasm
  • Drosophila Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • Ret protein, Drosophila