The variable subunit associated with protein phosphatase 2A0 defines a novel multimember family of regulatory subunits.
Two protein phosphatase 2A (PP2A) holoenzymes were isolated from rabbit skeletal muscle containing, in addition to the catalytic and PR65 regulatory subunits, proteins of apparent molecular masses of 61 and 56 kDa respectively. Both holoenzymes displayed low basal phosphorylase phosphatase activity, which could be stimulated by protamine to an extent similar to that of previously characterized PP2A holoenzymes. Protein micro-sequencing of tryptic peptides derived from the 61 kDa protein, termed PR61, yielded 117 residues of amino acid sequence. Molecular cloning by enrichment of specific mRNAs, followed by reverse transcription-PCR and cDNA library screening, revealed that this protein exists in multiple isoforms encoded by at least three genes, one of which gives rise to several splicing variants. Comparisons of these sequences with the available databases identified one more human gene and predicted another based on a rabbit cDNA-derived sequence, thus bringing the number of genes encoding PR61 family members to five. Peptide sequences derived from PR61 corresponded to the deduced amino acid sequences of either alpha or beta isoforms, indicating that the purified PP2A preparation was a mixture of at least two trimers. In contrast, the 56 kDa subunit (termed PR56) seems to correspond to the epsilon isoform of PR61. Several regulatory subunits of PP2A belonging to the PR61 family contain consensus sequences for nuclear localization and might therefore target PP2A to nuclear substrates.
Zolnierowicz
S
S
Friedrich Miescher-Institut, Basel, Switzerland.
Van Hoof
C
C
Andjelković
N
N
Cron
P
P
Stevens
I
I
Merlevede
W
W
Goris
J
J
Hemmings
B A
BA
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D005810:Multigene Family; D018482:Muscle, Skeletal / Q000201:enzymology; D010446:Peptide Fragments; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D054648:Protein Phosphatase 2; D011817:Rabbits; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D007527:Isoenzymes; D010446:Peptide Fragments; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2