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Updated: Apr 12, 2026

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
Published on: September 28, 2018
Intracellular enzymatic reducing systems control receptor tyrosine kinase signaling via PTP1B
Lucia Coppo1, Wenchao Zhao1, Qing Cheng1
1Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
None:
Protein tyrosine phosphatases (PTPs) counteract receptor tyrosine kinase (RTK) signaling. Inhibition of PTPs by oxidation can be reversed by cytosolic thioredoxin (TXN), but less is known about regulation of PTPs by glutathione (GSH)-driven glutaredoxins (GLRXs). Here, we thus assessed GLRX1, GLRX2, and/or TXN1 in regulation of CO2/bicarbonate- and H2O2-mediated oxidation of the physiologically important PTP1B. GLRXs and TXN1 synergistically maintained PTP1B activity, and modulating cellular levels of either GLRX1, GLRX2, or TXN1 gave strong effects on phosphorylation cascades triggered by epidermal growth factor (EGF) or platelet-derived growth factor (PDGF). Furthermore, transient intracellular interactions of PTP1B with GLRX1, GLRX2, and TXN1 were discovered within minutes after stimuli with either PDGF or EGF, coinciding with control of the corresponding RTK-driven phosphorylation cascades. We conclude that TXN1 and GLRXs are key regulators of PTP1B activity and thus control cellular responses to RTK stimulation.
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