THE SH2-LIKE AKT HOMOLOGY (AH) DOMAIN OF C-AKT IS PRESENT IN MULTIPLECOPIES IN THE GENOME OF VERTEBRATE AND INVERTEBRATE EUKARYOTES - CLONING AND CHARACTERIZATION OF THE DROSOPHILA-MELANOGASTER C-AKT HOMOLOG DAKT1

Citation
Tf. Franke et al., THE SH2-LIKE AKT HOMOLOGY (AH) DOMAIN OF C-AKT IS PRESENT IN MULTIPLECOPIES IN THE GENOME OF VERTEBRATE AND INVERTEBRATE EUKARYOTES - CLONING AND CHARACTERIZATION OF THE DROSOPHILA-MELANOGASTER C-AKT HOMOLOG DAKT1, Oncogene, 9(1), 1994, pp. 141-148
Citations number
32
Categorie Soggetti
Genetics & Heredity",Oncology
Journal title
ISSN journal
09509232
Volume
9
Issue
1
Year of publication
1994
Pages
141 - 148
Database
ISI
SICI code
0950-9232(1994)9:1<141:TSAH(D>2.0.ZU;2-#
Abstract
The Akf 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 contain s a domain related distantly to the SH2 domain of cytoplasmic tyrosine kinases and other signalling proteins, which we have named Akt homolo gy (AH) domain. Low stringency hybridization of a c-akt AH probe to a panel of genomic DNAs from vertebrate and invertebrate eucaryotes dete cted 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 rel ated gene (Dakt1). Comparison between the coding regions of c-akt and Dakt1 revealed 64.6% identity at the nucleotide level and 76.5% simila rity at the amino acid level. The highest degree of homology was detec ted in the AH domain (68.3% similarity at the amino acid level) and th e catalytic domain (83.3% similarity). Additional sequence comparisons revealed that the amino acid similarity between the catalytic domains of Dakt1 and the three known members of the Drosophila protein kinase C (PKC) family, Dpkc1, Dpkc2 and Dpkc3, is 68%, 63.6% and 67.1%, resp ectively. Dakt1 was mapped to Drosophila chromosome 3R 89BC. Its expre ssion is subject to developmental regulation with the highest levels d etected within the fourth hour of embryonic development. These results confirm that the AH domain of Akt defines new protein families in bot h vertebrate and invertebrate eucaryotes. The high degree of homology between the catalytic domains of Dakt1 and the three known members of the Drosophila PKC family suggests an evolutionarily conserved functio nal relationship between the members of the two families.