Structure, expression and chromosomal mapping of c-akt: Relationship to v-akt and its implications

Alfonso Bellacosa, Thomas F. Franke, M. Eugenia Gonzalez-Portal, Ketaki Datta, Takahiro Taguchi, John Gardner, Jin Quan Cheng, Joseph R. Testa, Philip N. Tsichlis

Research output: Contribution to journalArticlepeer-review

166 Scopus citations

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, Δp30)-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.

Original languageEnglish
Pages (from-to)745-754
Number of pages10
JournalOncogene
Volume8
Issue number3
StatePublished - Mar 1993

Keywords

  • 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
  • Proto-Oncogene Proteins c-akt/chemistry
  • Proto-Oncogene Proteins/chemistry
  • Proto-Oncogenes
  • Rats
  • Retroviridae Proteins, Oncogenic/chemistry
  • Transduction, Genetic

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