Interrogating PP1 Activity in the MAPK Pathway with Optimized PP1-Disrupting Peptides.
Chembiochem
; 20(1): 66-71, 2019 01 02.
Article
em En
| MEDLINE
| ID: mdl-30338897
ABSTRACT
Protein phosphatase-1 (PP1)-disrupting peptides (PDPs) are selective chemical modulators of PP1 that liberate the active PP1 catalytic subunit from regulatory proteins; thus allowing the dephosphorylation of nearby substrates. We have optimized the original cell-active PDP3 for enhanced stability, and obtained insights into the chemical requirements for stabilizing this 23-mer peptide for cellular applications. The optimized PDP-Nal was used to dissect the involvement of PP1 in the MAPK signaling cascade. Specifically, we have demonstrated that, in human osteosarcoma (U2OS) cells, phosphoMEK1/2 is a direct substrate of PP1, whereas dephosphorylation of phosphoERK1/2 is indirect and likely mediated through enhanced tyrosine phosphatase activity after PDP-mediated PP1 activation. Thus, as liberators of PP1 activity, PDPs represent a valuable tool for identifying the substrates of PP1 and understanding its role in diverse signaling cascades.
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Proteína Fosfatase 1
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article