Protein phosphatase 2A catalytic subunit is methyl-esterified at its carboxyl terminus by a novel methyltransferase.
In eukaryotic cells a number of different proteins with important regulatory functions are reversibly methyl-esterified at carboxyl-terminal prenylcysteine residues. These proteins include the low molecular weight GTP-binding proteins, the gamma-subunit of the heterotrimeric G-proteins, and the nuclear lamins. The methylating enzymes that catalyze this type of carboxyl methylation reaction are integral membrane proteins, and the methylated protein products tend to be membrane-associated. Analyses of protein carboxyl methylation in a wide range of vertebrate tissues revealed a major carboxyl-methylated protein that was clearly distinct from those that are modified at prenylcysteine groups (Volker, C., Miller, R.A., McCleary, W.R., Rao, A., Poenie, M., Backer, J.M., and Stock, J.B. (1991) J. Biol. Chem. 266, 21515-21522). This M(r) = 36,000 protein is localized to the cytosol. Unlike the prenylcysteine methyltransferases, the enzyme that catalyzes the methylation of the 36-kDa protein is found in the cytosol. The 36-kDa methylated protein has been purified from bovine brain. Sequence analysis of several peptides clearly shows that the protein is the catalytic subunit of protein phosphatase 2A. A soluble 40-kDa methyltransferase that catalyzes the reaction has also been purified.
Department of Molecular Biology, Princeton University, New Jersey 08544.
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D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002417:Cattle; D002848:Chromatography, DEAE-Cellulose; D007700:Kinetics; D046911:Macromolecular Substances; D008745:Methylation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D011496:Protein Methyltransferases / Q000302:isolation & purification / Q000378:metabolism*; D054648:Protein Phosphatase 2; D012436:S-Adenosylmethionine / Q000378:metabolism; D014316:Tritium
D046911:Macromolecular Substances; D010446:Peptide Fragments; D014316:Tritium; D012436:S-Adenosylmethionine; D011496:Protein Methyltransferases; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2