Intracellular enzymatic reducing systems control receptor tyrosine kinase signaling via PTP1B.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41961928.
- Also identified by DOI 10.1126/sciadv.adv5362 and PMC identifier 13068064.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 CO<sub>2</sub>/bicarbonate- and H<sub>2</sub>O<sub>2</sub>-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.
Medical subject headings
- Protein Tyrosine Phosphatase, Non-Receptor Type 1
- Signal Transduction
- Receptor Protein-Tyrosine Kinases
- Glutaredoxins