The SH2-like Akt homology (AH) domain of c-akt is present in multiple copies in the genome of vertebrate and invertebrate eucaryotes. Cloning and characterization of the Drosophila melanogaster c-akt homolog Dakt1.
The Akt proto-oncogene encodes a serine-threonine protein kinase whose carboxyterminal catalytic domain is closely related to the catalytic domains of all the known members of the protein kinase C (PKC) family. Akt, however, differs from PKC in its N-terminal region which contains a domain related distantly to the SH2 domain of cytoplasmic tyrosine kinases and other signalling proteins, which we have named Akt homology (AH) domain. Low stringency hybridization of a c-akt AH probe to a panel of genomic DNAs from vertebrate and invertebrate eucaryotes detected multiple DNA bands (perhaps multiple genes) in all tested species. Drosophila DNA contains at least three hybridizing DNA bands. One of them was cloned, and found by sequence analysis, to define an Akt related gene (Dakt1). Comparison between the coding regions of c-akt and Dakt1 revealed 64.6% identity at the nucleotide level and 76.5% similarity at the amino acid level. The highest degree of homology was detected in the AH domain (68.3% similarity at the amino acid level) and the catalytic domain (83.3% similarity). Additional sequence comparisons revealed that the amino acid similarity between the catalytic domains of Dkt1 and the three known members of the Drosophila protein kinase C (PKC) family, Dpkc1, Dpkc2 and Dpkc3, is 68%, 63.6% and 67.1%, respectively. Dakt1 was mapped to Drosophila chromosome 3R 89BC. Its expression is subject to developmental regulation with the highest levels detected within the fourth hour of embryonic development. These results confirm that the AH domain of Akt defines new protein families in both vertebrate and invertebrate eucaryotes. The high degree of homology between the catalytic domains of Dkt1 and the three known members of the Drosophila PKC family suggests an evolutionarily conserved functional relationship between the members of the two families.
Franke
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Fox Chase Cancer Center, Philadelphia, PA 19111.
Tartof
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Tsichlis
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics*; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D011493:Protein Kinase C / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D011519:Proto-Oncogenes; D017386:Sequence Homology, Amino Acid
D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; C494917:Akt1 protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C