Structure, expression and chromosomal mapping of c-akt: relationship to v-akt and its implications.
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.
Bellacosa
A
A
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Franke
T F
TF
Gonzalez-Portal
M E
ME
Datta
K
K
Taguchi
T
T
Gardner
J
J
Cheng
J Q
JQ
Testa
J R
JR
Tsichlis
P N
PN
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D004247:DNA / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D051058:Oncogene Protein v-akt; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000737:chemistry / Q000235:genetics*; D011519:Proto-Oncogenes; D051381:Rats; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry / Q000235:genetics*; D014161:Transduction, Genetic
D011518:Proto-Oncogene Proteins; D015682:Retroviridae Proteins, Oncogenic; D004247:DNA; C514862:Akt1 protein, mouse; C494920:Akt1 protein, rat; D051058:Oncogene Protein v-akt; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt