Reversible Methylation Of Protein Phosphatase 2a

PP2A has been shown to be methylated at the C-terminal leucine residue of the catalytic subunit by a specific 38 kDa methyltransferase (LCMT1) and demethylated by a specific 44-kDa methylesterase (PME-1). This reversible methylation does not seem to drastically change the PP2A activity but is shown to be a modulating factor in the binding of the third regulatory subunit. The structure of LCMT1 is solved and a model for the catalysis of the methylation reaction is presented.By purifying the PP2A-methylesterase, inactive dimeric (PP2Ai(D)) and trimeric (PP2Ai(T55)) holoenzymes were found to be associated with PME-1. Activation of this inactive complex is possible by the action of a ubiquitous and highly conserved activatory protein, PTPA. The function of PME-1 in this system seems to be independent of its demethylating activity. A large proportion of cellular PP2A is found methylated and the subject of regulation. Aberrant (de) methylation seems to be involved in the causes of diseases such as Alzheimer's disease and diabetes.