Subcellular Fate of the int-2 Oncoprotein Is Determined by Choice of Initiation Codon

Nature. 1990 Feb 15;343(6259):662-5. doi: 10.1038/343662a0.

Abstract

Fibroblast growth factors (FGFs) have been implicated in many aspects of cell growth and differentiation both in normal and neoplastic settings. For example, the mouse int-2 gene, which encodes an FGF-related product, is a frequent target of proviral activation in carcinomas induced by mouse mammary tumour virus, but apparently functions at discrete stages of normal embryonic development. Six classes of int-2 messenger RNA have been identified in embryonic cells, each of which is predicted to encode the same 245-amino-acid protein. But all known int-2 transcripts include sequences upstream of the AUG codon presumed to be the initiation codon. Here we report an additional N-terminally extended int-2 gene product initiated at an in-frame CUG codon. In COS-1 cells transiently transfected with appropriate int-2 complementary DNAs, the AUG-initiated product is found predominantly in the secretory pathway, whereas the CUG-initiated form is localized to the nucleus. These data indicate that the Int-2 oncoprotein could influence cellular behaviour by two distinct mechanisms.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • Cell Membrane / metabolism
  • Cell Nucleus / metabolism
  • Cloning, Molecular
  • Codon / genetics*
  • Fibroblast Growth Factor 3
  • Fibroblast Growth Factors / genetics*
  • Fibroblast Growth Factors / metabolism
  • Genetic Vectors
  • Mice
  • Microsomes / metabolism
  • Molecular Sequence Data
  • Mutation
  • Peptide Chain Initiation, Translational*
  • Protein Biosynthesis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • RNA, Messenger / genetics*
  • Rabbits
  • Restriction Mapping
  • Reticulocytes / metabolism
  • Subcellular Fractions / metabolism
  • Transfection

Substances

  • Codon
  • Fgf3 protein, mouse
  • Fibroblast Growth Factor 3
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Fibroblast Growth Factors