Redox regulation of PTEN and protein tyrosine phosphatases in H<sub>2</sub>O<sub>2</sub>‐mediated cell signaling

Cho, Seung-Hyun; Lee, Chang-Hun; Ahn, Younghee; Kim, Hyun-Jung; Kim, Hoeon; Ahn, Chiyoung; Yang, Kap‐Seok; Lee, Seung-Rock

doi:10.1016/s0014-5793(04)00112-7

Cited by 179 publications

(102 citation statements)

References 61 publications

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“…Experiments performed on purified proteins in vitro demonstrate that numerous proteins containing reactive thiolates, including peroxiredoxins, 65 GAPDH (glyceraldehyde-3-phosphate dehydrogenase) 66 and PTP1B (protein-tyrosine phosphatase 1B) 67 are converted to sulfenic acids and higher oxidation states when treated with oxidants such as hydrogen peroxide. In addition, many proteins have been identified as forming disulfide bonds in response to hydrogen peroxide treatment in Jurkat cell lysates.…”

Section: Incorporation Of Daz-1 Into Proteins In Cultured Human Cellsmentioning

confidence: 99%

A chemical approach for detecting sulfenic acid-modified proteins in living cells

et al. 2008

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Oxidation of the thiol functional group in cysteine (Cys-SH) to sulfenic (Cys-SOH), sulfinic (Cys-SO 2 H) and sulfonic acids (Cys-SO 3 H) is emerging as an important post-translational modification that can activate or deactivate the function of many proteins. Changes in thiol oxidation state have been implicated in a wide variety of cellular processes and correlate with disease states but are difficult to monitor in a physiological setting because of a lack of experimental tools. Here, we describe a method that enables live cell labeling of sulfenic acidmodified proteins. For this approach, we have synthesized the probe DAz-1, which is chemically selective for sulfenic acids and cell permeable. In addition, DAz-1 contains an azide chemical handle that can be selectively detected with phosphine reagents via the Staudinger ligation for identification, enrichment and visualization of modified proteins. Through a combination of biochemical, mass spectrometry and immunoblot approaches we characterize the reactivity of DAz-1 and highlight its utility for detecting protein sulfenic acids directly in mammalian cells. This novel method to isolate and identify sulfenic acid-modified proteins should be of widespread utility for elucidating signaling pathways and regulatory mechanisms that involve oxidation of cysteine residues.

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Section: Incorporation Of Daz-1 Into Proteins In Cultured Human Cellsmentioning

confidence: 99%

A chemical approach for detecting sulfenic acid-modified proteins in living cells

et al. 2008

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“…PTEN is oxidized during AA metabolism by COX-2 and 5-LOX PTEN, like the other members of the protein tyrosine phosphatase (PTP) family, has a signature motif of HCXXXXXR at the active site (Cho et al, 2004). This sequence lowers the pK a of the cysteine and facilitates its (Figure 3d, lane 3).…”

Section: Pten Activity Is Decreased Upon Aa Treatmentmentioning

confidence: 99%

Akt activation by arachidonic acid metabolism occurs via oxidation and inactivation of PTEN tumor suppressor

2007

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Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) enzymes are overexpressed during inflammation and multistage tumor progression in many neoplastic disorders including lung, breast and pancreatic cancers. Here we report that the tumor suppressor phosphatase and tensin homolog (PTEN) is oxidized and inactivated during arachidonic acid (AA) metabolism in pancreatic cancer cell lines expressing COX-2 or 5-LOX. Oxidation of PTEN decreases its phosphatase activity, favoring increased phosphatidylinositol 3,4,5-triphosphate production, activation of Akt and phosphorylation of downstream Akt targets including GSK-3b and S6K. These effects are recapitulated with pancreatic phospholipase A 2 , which hydrolyses the release of membrane-bound AA. Interference with PTEN's physiological antagonism of signals from growth factors, insulin and oncogenes may confer risk for hypertrophic or neoplastic diseases associated with chronic inflammation or unwarranted oxidative metabolism of essential fatty acids.

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“…In the latter case, oxidants may act by direct thiol modification or indirectly by concomitant inhibition of protein tyrosine phosphatase, which can lead to phosphorylation and sustained activation of tyrosine kinase [49]. Importantly, oxidative modifications of thiols in tyrosine phosphatases are reversed by intracellular reducing molecules such as Trx, Grx and GSH [50]. In our experimental model therefore, it may be postulated that diamide inhibited I peak and I ss through activation of tyrosine kinases and/or inhibition of tyrosine phosphatases, and that these effects were reversed by oxidoreductase systems stimulated by DCA.…”

Section: Differential Control Of K + Currents By Thioredoxin and Glutmentioning

confidence: 99%

Oxidoreductase regulation of Kv currents in rat ventricle

Liang

et al. 2008

Journal of Molecular and Cellular Cardiology

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Oxidative stress contributes to the arrhythmogenic substrate created by myocardial ischemiareperfusion partly through a shift in cell redox state, a key modulator of protein function. The activity of many oxidation-sensitive proteins is controlled by oxidoreductase systems that regulate the redox state of cysteine thiol groups, but the impact of these systems on ion channel function is not well defined. Thus, we examined the roles of the thioredoxin and glutaredoxin systems in controlling K + channels in the ventricle. An oxidative shift in redox state was elicited in isolated rat ventricular myocytes by brief exposure to diamide, a thiol-specific, membrane-permeable oxidant. Voltageclamp studies showed that diamide decreased peak outward K + current (I peak ) evoked by depolarizing test pulses by 41% (+60 mV; p<0.05) while steady-state outward current (I ss ) measured at the end of the test pulse was decreased by 45% (p<0.05). These electrophysiological effects were not prevented by protein kinase C blockers, but the tyrosine kinase inhibitors genistein or lavendustin A blocked the suppression of both K + currents by diamide. Moreover, inhibition of I peak and I ss by diamide was reversed by dichloroacetate and an insulin-mimetic. The effect of dichloroacetate to normalize I peak after diamide was blocked by the thioredoxin system inhibitors auranofin or 13-cisretinoic acid, but I ss was not affected by either compound. A pan-specific inhibitor of glutaredoxin and thioredoxin systems, 1,3-bis-(2-chloroethyl)-1-nitrosourea, also blocked the dichloroacetate effect on I peak but only partially inhibited the recovery of I ss . These data suggest that acute regulation of cardiac K + channels by oxidoreductase systems is mediated by redox-sensitive tyrosine kinase/ phosphatase pathways. The pathways controlling I peak channels are targets of the thioredoxin system whereas those regulating I ss channels are likely controlled by the glutaredoxin system. Thus, cardiac oxidoreductase systems may be important regulators of ion channels affected by pathogenic oxidative stress.

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Redox regulation of PTEN and protein tyrosine phosphatases in H₂O₂‐mediated cell signaling

Cited by 179 publications

References 61 publications

A chemical approach for detecting sulfenic acid-modified proteins in living cells

A chemical approach for detecting sulfenic acid-modified proteins in living cells

Akt activation by arachidonic acid metabolism occurs via oxidation and inactivation of PTEN tumor suppressor

Oxidoreductase regulation of Kv currents in rat ventricle

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Redox regulation of PTEN and protein tyrosine phosphatases in H2O2‐mediated cell signaling

Cited by 179 publications

References 61 publications

A chemical approach for detecting sulfenic acid-modified proteins in living cells

A chemical approach for detecting sulfenic acid-modified proteins in living cells

Akt activation by arachidonic acid metabolism occurs via oxidation and inactivation of PTEN tumor suppressor

Oxidoreductase regulation of Kv currents in rat ventricle

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Redox regulation of PTEN and protein tyrosine phosphatases in H₂O₂‐mediated cell signaling