Interrogating PP1 activity in the MAPK pathway with optimized PP1-disrupting peptides

• Verfasst von: Wang, Yansong [VerfasserIn]
• Verfasst von: Hörmann, Bernhard [VerfasserIn]
• Titel: Interrogating PP1 activity in the MAPK pathway with optimized PP1-disrupting peptides
• Verf.angabe: Yansong Wang, Bernhard Hoermann, Karolina Pavic, Malgorzata Trebacz, Pablo Rios, Maja Köhn
• Jahr: 2019
• Jahr des Originals: 2018
• Umfang: 6 S.
• Fussnoten: First published: 19 October 2018 ; Gesehen am 19.06.2019
• Titel Quelle: Enthalten in: ChemBioChem
• Ort Quelle: Weinheim : Wiley-VCH, 2000
• Jahr Quelle: 2019
• Band/Heft Quelle: 20(2019), 1, Seite 66-71
• ISSN Quelle: 1439-7633
• DOI: doi:10.1002/cbic.201800541
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: activators
• Sach-SW: amino acids
• Sach-SW: kinases
• Sach-SW: peptides
• Sach-SW: phosphorylation
• K10plus-PPN: 1667663135

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.