Deletion of an N-terminal regulatory domain of the c-abl tyrosine kinase activates its oncogenic potential

EMBO J. 1989 Jan;8(1):137-47.

Abstract

The requirements for the oncogenic conversion of the c-abl proto-oncogene have been determined by the expression of N-terminal deleted forms and viral gag-fused forms of the c-abl proteins from a selectable retroviral vector. To activate the transforming potential of c-abl, it is necessary that (i) specific N-terminal amino acids are deleted to release the kinase from negative regulation in vivo; (ii) an N-terminal myristylation site is part of the activated kinase; (iii) the fatty-acylated, activated kinase is overproduced. The N-terminal amino acids found to be necessary for the cellular inhibition of c-abl tyrosine phosphorylation are part of a homologous region present in many non-receptor tyrosine kinases, the v-crk oncogene and phospholipase C-II. Overproduction of a deregulated and myristylated c-abl tyrosine kinase induces the transformation of NIH 3T3 cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abelson murine leukemia virus / genetics
  • Amino Acid Sequence
  • Cell Line
  • Cell Transformation, Neoplastic / enzymology*
  • Chromosome Deletion
  • Enzyme Activation
  • Fibroblasts
  • Fusion Proteins, bcr-abl
  • Gene Products, gag
  • Moloney murine leukemia virus / genetics
  • Neoplasm Proteins / physiology
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-abl
  • Recombinant Fusion Proteins / metabolism
  • Retroviridae Proteins / genetics
  • Viral Proteins / physiology

Substances

  • Gene Products, gag
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • Retroviridae Proteins
  • Viral Proteins
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl
  • Proto-Oncogene Proteins c-abl