Targeted Disruption of the PME-1 Gene Causes Loss of Demethylated PP2A and Perinatal Lethality in MiceReportar como inadecuado




Targeted Disruption of the PME-1 Gene Causes Loss of Demethylated PP2A and Perinatal Lethality in Mice - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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.



Autor: Silvia Ortega-Gutiérrez, Donmienne Leung, Scott Ficarro, Eric C. Peters, Benjamin F. Cravatt

Fuente: http://plos.srce.hr/



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