The myeloperoxidase-derived oxidant hypothiocyanous acid inhibits protein tyrosine phosphatases via oxidation of key cysteine residues

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The myeloperoxidase-derived oxidant hypothiocyanous acid inhibits protein tyrosine phosphatases via oxidation of key cysteine residues. / Cook, Naomi L.; Moeke, Cassidy H.; Fantoni, Luca I.; Pattison, David I.; Davies, Michael J.

In: Free Radical Biology & Medicine, Vol. 90, 01.01.2016, p. 195-205.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Cook, NL, Moeke, CH, Fantoni, LI, Pattison, DI & Davies, MJ 2016, 'The myeloperoxidase-derived oxidant hypothiocyanous acid inhibits protein tyrosine phosphatases via oxidation of key cysteine residues', Free Radical Biology & Medicine, vol. 90, pp. 195-205. https://doi.org/10.1016/j.freeradbiomed.2015.11.025

APA

Cook, N. L., Moeke, C. H., Fantoni, L. I., Pattison, D. I., & Davies, M. J. (2016). The myeloperoxidase-derived oxidant hypothiocyanous acid inhibits protein tyrosine phosphatases via oxidation of key cysteine residues. Free Radical Biology & Medicine, 90, 195-205. https://doi.org/10.1016/j.freeradbiomed.2015.11.025

Vancouver

Cook NL, Moeke CH, Fantoni LI, Pattison DI, Davies MJ. The myeloperoxidase-derived oxidant hypothiocyanous acid inhibits protein tyrosine phosphatases via oxidation of key cysteine residues. Free Radical Biology & Medicine. 2016 Jan 1;90:195-205. https://doi.org/10.1016/j.freeradbiomed.2015.11.025

Author

Cook, Naomi L. ; Moeke, Cassidy H. ; Fantoni, Luca I. ; Pattison, David I. ; Davies, Michael J. / The myeloperoxidase-derived oxidant hypothiocyanous acid inhibits protein tyrosine phosphatases via oxidation of key cysteine residues. In: Free Radical Biology & Medicine. 2016 ; Vol. 90. pp. 195-205.

Bibtex

@article{a323a7c2f4af4bfda3ac31094ae85a73,
title = "The myeloperoxidase-derived oxidant hypothiocyanous acid inhibits protein tyrosine phosphatases via oxidation of key cysteine residues",
abstract = "Phosphorylation of protein tyrosine residues is critical to cellular processes, and is regulated by kinases and phosphatases (PTPs). PTPs contain a redox-sensitive active site Cys residue, which is readily oxidized. Myeloperoxidase, released from activated leukocytes, catalyzes thiocyanate ion (SCN-) oxidation by H2O2 to form hypothiocyanous acid (HOSCN), an oxidant that targets Cys residues. Dysregulated phosphorylation and elevated MPO levels have been associated with chronic inflammatory diseases where HOSCN can be generated. Previous studies have shown that HOSCN inhibits isolated PTP1B and induces cellular dysfunction in cultured macrophage-like cells. The present study extends this previous work and shows that physiologically-relevant concentrations of HOSCN alter the activity and structure of other members of the wider PTP family (including leukocyte antigen-related PTP, PTP-LAR; T-cell PTP, TC-PTP; CD45 and Src homology phosphatase-1, Shp-1) by targeting Cys residues. Isolated PTP activity, and activity in lysates of human monocyte-derived macrophages (HMDM) was inhibited by 0-100 μM HOSCN with this being accompanied by reversible oxidation of Cys residues, formation of sulfenic acids or sulfenyl-thiocyanates (detected by Western blotting, and LC-MS as dimedone adducts), and structural changes. LC-MS/MS peptide mass-mapping has provided data on the modified Cys residues in PTP-LAR. This study indicates that inflammation-induced oxidants, and particularly myeloperoxidase-derived species, can modulate the activity of multiple members of the PTP superfamily via oxidation of Cys residues to sulfenic acids. This alteration of the balance of PTP/kinase activity may perturb protein phosphorylation and disrupt cell signaling with subsequent induction of apoptosis at sites of inflammation.",
keywords = "Inflammation, Myeloperoxidase, Phosphorylation, Protein oxidation, Protein tyrosine phosphatases, Sulfenic acid, Thiol",
author = "Cook, {Naomi L.} and Moeke, {Cassidy H.} and Fantoni, {Luca I.} and Pattison, {David I.} and Davies, {Michael J.}",
year = "2016",
month = "1",
day = "1",
doi = "10.1016/j.freeradbiomed.2015.11.025",
language = "English",
volume = "90",
pages = "195--205",
journal = "Free Radical Biology & Medicine",
issn = "0891-5849",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - The myeloperoxidase-derived oxidant hypothiocyanous acid inhibits protein tyrosine phosphatases via oxidation of key cysteine residues

AU - Cook, Naomi L.

AU - Moeke, Cassidy H.

AU - Fantoni, Luca I.

AU - Pattison, David I.

AU - Davies, Michael J.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Phosphorylation of protein tyrosine residues is critical to cellular processes, and is regulated by kinases and phosphatases (PTPs). PTPs contain a redox-sensitive active site Cys residue, which is readily oxidized. Myeloperoxidase, released from activated leukocytes, catalyzes thiocyanate ion (SCN-) oxidation by H2O2 to form hypothiocyanous acid (HOSCN), an oxidant that targets Cys residues. Dysregulated phosphorylation and elevated MPO levels have been associated with chronic inflammatory diseases where HOSCN can be generated. Previous studies have shown that HOSCN inhibits isolated PTP1B and induces cellular dysfunction in cultured macrophage-like cells. The present study extends this previous work and shows that physiologically-relevant concentrations of HOSCN alter the activity and structure of other members of the wider PTP family (including leukocyte antigen-related PTP, PTP-LAR; T-cell PTP, TC-PTP; CD45 and Src homology phosphatase-1, Shp-1) by targeting Cys residues. Isolated PTP activity, and activity in lysates of human monocyte-derived macrophages (HMDM) was inhibited by 0-100 μM HOSCN with this being accompanied by reversible oxidation of Cys residues, formation of sulfenic acids or sulfenyl-thiocyanates (detected by Western blotting, and LC-MS as dimedone adducts), and structural changes. LC-MS/MS peptide mass-mapping has provided data on the modified Cys residues in PTP-LAR. This study indicates that inflammation-induced oxidants, and particularly myeloperoxidase-derived species, can modulate the activity of multiple members of the PTP superfamily via oxidation of Cys residues to sulfenic acids. This alteration of the balance of PTP/kinase activity may perturb protein phosphorylation and disrupt cell signaling with subsequent induction of apoptosis at sites of inflammation.

AB - Phosphorylation of protein tyrosine residues is critical to cellular processes, and is regulated by kinases and phosphatases (PTPs). PTPs contain a redox-sensitive active site Cys residue, which is readily oxidized. Myeloperoxidase, released from activated leukocytes, catalyzes thiocyanate ion (SCN-) oxidation by H2O2 to form hypothiocyanous acid (HOSCN), an oxidant that targets Cys residues. Dysregulated phosphorylation and elevated MPO levels have been associated with chronic inflammatory diseases where HOSCN can be generated. Previous studies have shown that HOSCN inhibits isolated PTP1B and induces cellular dysfunction in cultured macrophage-like cells. The present study extends this previous work and shows that physiologically-relevant concentrations of HOSCN alter the activity and structure of other members of the wider PTP family (including leukocyte antigen-related PTP, PTP-LAR; T-cell PTP, TC-PTP; CD45 and Src homology phosphatase-1, Shp-1) by targeting Cys residues. Isolated PTP activity, and activity in lysates of human monocyte-derived macrophages (HMDM) was inhibited by 0-100 μM HOSCN with this being accompanied by reversible oxidation of Cys residues, formation of sulfenic acids or sulfenyl-thiocyanates (detected by Western blotting, and LC-MS as dimedone adducts), and structural changes. LC-MS/MS peptide mass-mapping has provided data on the modified Cys residues in PTP-LAR. This study indicates that inflammation-induced oxidants, and particularly myeloperoxidase-derived species, can modulate the activity of multiple members of the PTP superfamily via oxidation of Cys residues to sulfenic acids. This alteration of the balance of PTP/kinase activity may perturb protein phosphorylation and disrupt cell signaling with subsequent induction of apoptosis at sites of inflammation.

KW - Inflammation

KW - Myeloperoxidase

KW - Phosphorylation

KW - Protein oxidation

KW - Protein tyrosine phosphatases

KW - Sulfenic acid

KW - Thiol

U2 - 10.1016/j.freeradbiomed.2015.11.025

DO - 10.1016/j.freeradbiomed.2015.11.025

M3 - Journal article

VL - 90

SP - 195

EP - 205

JO - Free Radical Biology & Medicine

JF - Free Radical Biology & Medicine

SN - 0891-5849

ER -

ID: 152247625