Hy. Xie et S. Clarke, PROTEIN PHOSPHATASE-2A IS REVERSIBLY MODIFIED BY METHYL ESTERIFICATION AT ITS C-TERMINAL LEUCINE RESIDUE IN BOVINE BRAIN, The Journal of biological chemistry, 269(3), 1994, pp. 1981-1984
We have recently described a novel protein carboxyl methylation system
that results in the reversible modification of a 36-kDa polypeptide c
omponent of a 178-kDa protein in the cytosol of a variety of eucaryoti
c cells. This reaction, catalyzed by a cytosolic 40-kDa methyltransfer
ase, results in the methyl esterification of the alpha-carboxyl group
of the C-terminal leucine residue. We have now purified the major meth
ylated 36-kDa polypeptide from bovine brain. N-terminal sequence analy
sis of a tryptic fragment of this polypeptide revealed identity to the
catalytic subunit of protein phosphatase 2A. This enzyme exists in th
e cell predominantly as a trimeric 151-kDa native species containing t
he 36-kDa catalytic polypeptide that terminates in a leucine residue.
We then fractionated bovine brain cytosolic extracts to separate the m
ajor phosphatase isoforms 2A1 and 2A2 and found that both could be met
hylated by a partially purified preparation of the methyltransferase.
A synthetic C-terminal octapeptide based on the sequence of the 36-kDa
catalytic subunit is neither a substrate nor an inhibitor of this met
hyltransferase, suggesting that this enzyme recognizes aspects of the
tertiary and/or quaternary structure of the native phosphatase. Becaus
e this modification reaction is readily reversible in extracts, it may
represent a novel strategy of the cell to modulate the function of th
is protein phosphatase.