Phosphatase Control by Methylation

Abstract

Protein phosphatase 2A (PP2A) is involved in many diverse cellular processes. Target specificity and activity are regulated by the interaction of the catalytic heterodimer of PP2A with regulatory subunits. This interaction is further influenced by posttranslational modifications. Yu et al. demonstrate, through a combination of studies in vivo in transfected cells and in vitro, that the C subunit of the PP2A catalytic heterodimer is methylated. The PP2A catalytic A-C heterodimer is methylated at the COOH-terminal leucine (L309) of the C subunit. Methylation enhances the ability of PP2A A-C to interact with the regulatory subunit Bα, but does not influence the interaction with other regulatory subunits (striatin, SG2NA, or the polyomavirus middle tumor antigen). Methylation was decreased by mutation of tyrosine 307, but not threonine 304. Thus, methylation of the COOH-terminus of the C subunit of PP2A may represent a molecular mechanism for regulating PP2A activity. X. X. Yu, X. Du, C. S. Moreno, R. E. Green, E. Ogris, Q. Feng, L. Chou, M. J. McQuiod, D. C. Pallas, Methylation of the protein phosphatase 2A catalytic subunit is essential for association of Bα regulatory subunit but not SG2NA, striatin, or polyomavirus middle tumor antigen. Mol. Biol. Cell 12 , 185-199 (2001). [Abstract] [Full Text]