IDENTIFICATION OF MEMBERS OF THE PROTEIN PHOSPHATASE-1 GENE FAMILY IN THE RAT AND ENHANCED EXPRESSION OF PROTEIN PHOSPHATASE-1-ALPHA GENE IN RAT HEPATOCELLULAR CARCINOMAS

We isolated four kinds of cDNA clones of isotypes of catalytic subunits of protein phosphatase 1 (PP-1) from rat liver and testis cDNA libraries. For the cloning, cDNA fragments of dis2m1 and dis2m2, which encode mouse PP-1 catalytic subunits, were used as probes. Two of the four isotypes were thought to be derived from the same gene and produced by alternative splicing. Based on the comparative study of their nucleotide and deduced amino acid sequences with those reported, these cDNA clones were named rat PP-1-alpha, PP-1-gamma-1, PP-1-gamma-2 and PP-1-delta. The deduced amino acid sequences of these four cDNA clones showed about 90% identity. Their amino-terminal regions were highly conserved, and their differences were mainly in the carboxy-terminal regions. Furthermore, several amino acids located in the middle regions of the peptides were conserved in all the isotypes of the catalytic subunits of PP-1, PP-2A, PP-2B and PP-2C. These conserved regions are suggested to be the functional domains of the catalytic subunits of protein phosphatases. Rat hepatocellular carcinomas induced by a food mutagen, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline showed increased expression of PP-1-alpha, but no increased expression of PP-1-gamma-1, PP-1-gamma-2 or PP-1-delta. Involvement of PP-1-alpha in hepatocarcinogenesis or in hepatic cell proliferation was suspected.