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Regulation of PTP1B activation through disruption of redox-complex formation


We have identified a molecular interaction between the reversibly oxidized form of protein tyrosine phosphatase 1B (PTP1B) and 14-3-3ζ that regulates PTP1B activity. Destabilizing the transient interaction between 14-3-3ζ and PTP1B prevented PTP1B inactivation by reactive oxygen species and decreased epidermal growth factor receptor phosphorylation. Our data suggest that destabilizing the interaction between 14-3-3ζ and the reversibly oxidized and inactive form of PTP1B may establish a path to PTP1B activation in cells.

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Fig. 1: The exposed pTyr recognition loop of PTP1B-OX interacts with 14-3-3ζ.
Fig. 2: Destabilizing the association between 14-3-3ζ and PTP1B-OX prevents PTP1B inactivation and decreases EGFR phosphorylation.

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Data availability

The structures of reduced PTP1B (PDB code: 2HNQ) and PTP1B-OX (PDB code: 1OEM) were used for the accessible surface area calculation. The MS data in Supplementary Tables 1 and 2 will be made available in the PRoteomics IDEntifications database.


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We thank H. Fu for providing the 14-3-3ζ plasmid. This research was supported by the National Institutes of Health grant no. HL138605 and the American Heart Association grant no. 17GRNT33700265 to B.B. and National Institutes of Health grant no. GM55989 to N.K.T. B.B. is also grateful for support from the following foundations: the Heart and Stroke Foundation of Canada and SUNY Research Foundation. B.B. is an FRQS Research Scholar and A.B. was the recipient of a scholarship from the FRQS.

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A.D.L., A.B., S.M.C., A.K., G.C., S.H.M.R. and B.B. performed experiments and analyzed data. K.D.R. and D.J.P. acquired and analyzed MS data. S.J.K. performed structural analysis and modeling. F.Z. and R.J.L. acquired and analyzed SPR data. N.K.T. and B.B. wrote the manuscript.

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Correspondence to Benoit Boivin.

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Supplementary Tables 1 and 2 and Figs. 1–21.

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Londhe, A.D., Bergeron, A., Curley, S.M. et al. Regulation of PTP1B activation through disruption of redox-complex formation. Nat Chem Biol 16, 122–125 (2020).

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