| First Author | Ortega-Gutiérrez S | Year | 2008 |
| Journal | PLoS One | Volume | 3 |
| Issue | 7 | Pages | e2486 |
| PubMed ID | 18596935 | Mgi Jnum | J:138002 |
| Mgi Id | MGI:3803538 | Doi | 10.1371/journal.pone.0002486 |
| Citation | Ortega-Gutierrez S, et al. (2008) Targeted disruption of the PME-1 gene causes loss of demethylated PP2A and perinatal lethality in mice. PLoS One 3(7):e2486 |
| abstractText | BACKGROUND: Phosphoprotein phosphatase 2A (PP2A), a major serine-threonine protein phosphatase in eukaryotes, is an oligomeric protein comprised of structural (A) and catalytic (C) subunits to which a variable regulatory subunit (B) can associate. The C subunit contains a methyl ester post-translational modification on its C-terminal leucine residue, which is removed by a specific methylesterase (PME-1). Methylesterification is thought to control the binding of different B subunits to AC dimers, but little is known about its physiological significance in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that targeted disruption of the PME-1 gene causes perinatal lethality in mice, a phenotype that correlates with a virtually complete loss of the demethylated form of PP2A in the nervous system and peripheral tissues. Interestingly, PP2A catalytic activity over a peptide substrate was dramatically reduced in PME-1(-/-) tissues, which also displayed alterations in phosphoproteome content. CONCLUSIONS: These findings suggest a role for the demethylated form of PP2A in maintenance of enzyme function and phosphorylation networks in vivo. |
