DROSOPHILA CONTAINS 3 GENES THAT ENCODE DISTINCT ISOFORMS OF PROTEIN PHOSPHATASE-1

The sequences of two Drosophila and one rabbit protein phosphatase (PP) 1 catalytic subunits were determined from their cDNA. The sequence of Drosophila PP1-alpha1 was deduced from a 2.2-kb cDNA purified from an embryonic cDNA library, while that for Drosophila PP1-beta was obtained from overlapping clones isolated from both a head cDNA library and an eye imaginal disc cDNA library. The gene for Drosophila PP1-alpha1 is at 96A2-5 on chromosome 3 and encodes a protein of 327 amino acids with a calculated molecular mass of 37.3 kDa. The gene for Drosophila PP1-beta is localized at 9C1-2 on the X chromosome and encodes a protein of 330 amino acids with a predicted molecular mass of 37.8 kDa. PP1-alpha1 shows 96% amino acid sequence identity to PP1-alpha2 (302 amino acids), an isoform whose gene is located in the 87B6-12 region of chromosome 3 [Dombradi, V., Axton, J. M., Glover, D. M. Cohen, P. T. W. (1989) Eur. J. Biochem. 183, 603-610]. PP1-beta shows 85% identity to PP1-alpha1 and PP1-alpha2 over the 302 homologous amino acids. These results demonstrate that at least three genes are present in Drosophila that encode different isoforms of PP1. Drosophila PP1-alpha1 and PP1-beta show 89% amino acid sequence identity to rabbit PP1-alpha (330 amino acids) [Cohen, P. T. W. (1988) FEBS Lett. 232, 17-23] and PP1-beta (327 amino acids), respectively, demonstrating that the structures of both isoforms are among the most conserved proteins known throughout the evolution of the animal kingdom. The presence of characteristic structural differences between PP1-alpha and PP1-beta, which have been preserved from insects to mammals, implies that the alpha and beta isoforms may have distinct biological functions.