Structure, Expression and Chromosomal Mapping of C-Akt: Relationship to V-Akt and Its Implications

Oncogene. 1993 Mar;8(3):745-54.

Abstract

Sequence analysis of a nearly full-length murine c-akt cDNA clone and comparison with v-akt revealed the following: (a) The entire coding region of c-akt is identical to that of v-akt with the exception of five G to A transitions that do not alter the reading frame. The 3' untranslated regions of v-akt and c-akt are also identical with the exception of three single-base differences. (b) The recombination event that gave rise to v-akt occurred between the virus at nucleotide 785 from the Gag ATG codon and the 5' untranslated region of c-akt to 60 bp 5' from the c-akt ATG codon. (c) Three nucleotides absent from both Gag and c-akt were inserted at the junction between the two genes. The outcome of these events was to place, in frame, a 63-bp fragment between Gag and Akt. The resulting v-akt oncogene is predicted to encode a tripartite Gag (p12, p15, delta p30)-X-c-akt protein product. The c-akt protein contains, starting from its amino terminus, a src homology 2-like (SH2-like) domain, a domain rich in glutamic acid residues, part of which is predicted to form an amphipathic helix, and a kinase domain encoding a serine-threonine kinase with high degree of homology to members of the protein kinase C (PKC) family. The mouse c-akt is 90% homologous to human AKT1/RAC at the nucleic acid level and 98% homologous at the amino acid level. c-akt in the mouse is composed of 13 exons. The first exon contains a 5' untranslated GC-rich region. Since the recombination that gave rise to v-akt occurred with the 5' untranslated region, we hypothesize that the transduction of c-akt was preceded by provirus insertion upstream from or within the 5' untranslated region and in the same transcriptional orientation as the gene. c-akt was mapped by fluorescence in situ hybridization (FISH) to mouse chromosome 12 and rat chromosome 6 in close proximity to the Igh locus.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chromosome Mapping*
  • DNA / chemistry
  • Female
  • Gene Expression*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Oncogene Protein v-akt
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / genetics
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-akt / chemistry
  • Proto-Oncogene Proteins c-akt / genetics*
  • Proto-Oncogenes*
  • Rats
  • Retroviridae Proteins, Oncogenic / chemistry
  • Retroviridae Proteins, Oncogenic / genetics*
  • Transduction, Genetic

Substances

  • Proto-Oncogene Proteins
  • Retroviridae Proteins, Oncogenic
  • DNA
  • Akt1 protein, mouse
  • Akt1 protein, rat
  • Oncogene Protein v-akt
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt

Associated data

  • GENBANK/X65687