Bicarbonate is essential for protein-tyrosine phosphatase 1B (PTP1B) oxidation and cellular signaling through EGF-triggered phosphorylation cascades.

ABSTRACT: Protein-tyrosine phosphatases (PTPs) counteract protein tyrosine phosphorylation and cooperate with receptor-tyrosine kinases in the regulation of cell signaling. PTPs need to undergo oxidative inhibition for activation of cellular cascades of protein-tyrosine kinase phosphorylation following growth factor stimulation. It has remained enigmatic how such oxidation can occur in the presence of potent cellular reducing systems. Here, using in vitro biochemical assays with purified, recombinant protein, along with experiments in the adenocarcinoma cell line A431, we discovered that bicarbonate, which reacts with H₂O₂ to form the more reactive peroxymonocarbonate, potently facilitates H₂O₂-mediated PTP1B inactivation in the presence of thioredo

SUBMITTER: Dagnell M 

PROVIDER: S-EPMC6699834 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature