Regulation of PTP1B activation through disruption of redox-complex formation

Londhe, Avinash; Bergeron, Alexandre; Curley, Stephanie M.; Zhang, Fuming; Rivera, Keith; Kannan, Akaash; Coulis, Gérald; Rizvi, Syed Husain Mustafa; Kim, Seung Jun; Pappin, Darryl; Tonks, Nicholas K.; Linhardt, Robert J.; Boivin, Benoît

doi:10.1038/s41589-019-0433-0

Cited by 25 publications

(22 citation statements)

References 30 publications

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“…Therefore, cellular HCO 3 − levels may dictate the total phosphotyrosine levels observed in cells after stimulation with EGF, and correlate with PTP1B oxidation [ 36 ]. Furthermore, 14-3-3 proteins are necessary to stabilise the oxidised form of PTP1B and prevent its re-activation [ 111 ].…”

Section: Insulin-mediated H 2 O 2 Generation Regulates Insulin Signallingmentioning

confidence: 99%

Redox regulation of the insulin signalling pathway

Lennicke

Cochemé

2021

Redox Biology

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The peptide hormone insulin is a key regulator of energy metabolism, proliferation and survival. Binding of insulin to its receptor activates the PI3K/AKT signalling pathway, which mediates fundamental cellular responses. Oxidants, in particular H 2 O 2 , have been recognised as insulin-mimetics. Treatment of cells with insulin leads to increased intracellular H 2 O 2 levels affecting the activity of downstream signalling components, thereby amplifying insulin-mediated signal transduction. Specific molecular targets of insulin-stimulated H 2 O 2 include phosphatases and kinases, whose activity can be altered via redox modifications of critical cysteine residues. Over the past decades, several of these redox-sensitive cysteines have been identified and their impact on insulin signalling evaluated. The aim of this review is to summarise the current knowledge on the redox regulation of the insulin signalling pathway.

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Section: Insulin-mediated H 2 O 2 Generation Regulates Insulin Signallingmentioning

confidence: 99%

Redox regulation of the insulin signalling pathway

Lennicke

Cochemé

2021

Redox Biology

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“…Reciprocally, p53 regulates the expression of antioxidant genes to maintain cellular redox balance [79]. Other transcription factors, such as AMP-activated protein kinase (AMPK), activator protein 1 (AP-1), heat shock factor 1 (HSF1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), uncoupling protein (UCP), and protein-tyrosine phosphatase 1B (PTP1B), also contribute to redox status [80][81][82][83][84][85]. However, the extents to which individual members of the above network of antioxidant transcription factors are differentially activated by oxidative stress are uncertain, although it is improbable that all of them are activated simultaneously.…”

Section: Intracellular Clearance Of Rosmentioning

confidence: 99%

Targeting Reactive Oxygen Species Capacity of Tumor Cells with Repurposed Drug as an Anticancer Therapy

Wang

Sun

Huang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Accumulating evidence shows that elevated levels of reactive oxygen species (ROS) are associated with cancer initiation, growth, and response to therapies. As concentrations increase, ROS influence cancer development in a paradoxical way, either triggering tumorigenesis and supporting the proliferation of cancer cells at moderate levels of ROS or causing cancer cell death at high levels of ROS. Thus, ROS can be considered an attractive target for therapy of cancer and two apparently contradictory but virtually complementary therapeutic strategies for the regulation of ROS to treat cancer. Despite tremendous resources being invested in prevention and treatment for cancer, cancer remains a leading cause of human deaths and brings a heavy burden to humans worldwide. Chemotherapy remains the key treatment for cancer therapy, but it produces harmful side effects. Meanwhile, the process of de novo development of new anticancer drugs generally needs increasing cost, long development cycle, and high risk of failure. The use of ROS-based repurposed drugs may be one of the promising ways to overcome current cancer treatment challenges. In this review, we briefly introduce the source and regulation of ROS and then focus on the status of repurposed drugs based on ROS regulation for cancer therapy and propose the challenges and direction of ROS-mediated cancer treatment.

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“…Unlike the original 3-step cysteinyl labeling assay, which is designed to biotinylate reversibly oxidized PTPs at pH 5.5, the direct cysteinyl labeling assay is a 2-step assay optimized to tag active PTPs in cell lysates ( Fig. 6A and B; Londhe et al, 2020). This direct cysteinyl labeling approach also relies on the reactivity of the active site cysteinyl side chain of PTPs towards a biotinylated iodoacetyl-polyethylene glycol (IAP) probe at pH 5.5.…”

Section: Measurement Of Active Ptps Via Direct Cysteinyl Labelingmentioning

confidence: 99%

“…The methods described herein were specifically developed to measure the dynamic reactivation of reversibly oxidized PTP1B in cells that were stimulated with EGF (Londhe et al, 2020). Our approach, which relies on conditions that minimize artefactual oxidation of PTPs and on the absence of any reducing agent, is similar in some ways to the cysteinyl labeling assay for identifying reversibly oxidized PTPs in cells Boivin et al, 2008).…”

Section: Commentary Background Informationmentioning

confidence: 99%

“…The first protocol that we describe is designed to quantitatively assess endogenous catalytic activity of specific PTPs in cells stimulated by growth factors. This method is a detailed description of the endogenous PTP-activity assay that we recently used to study how a protein complex stabilizes the reversibly oxidized form of PTP1B following cell stimulation with epidermal growth factor (EGF; Londhe et al, 2020). This technique is challenging in several ways.…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Activity Assays to Quantitatively Assess the Endogenous Reversible Oxidation State of Protein Tyrosine Phosphatases in Cells

Londhe

Rizvi

Boivin

2020

CP Chemical Biology

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The reversible oxidation of protein tyrosine phosphatases (PTPs) impairs their ability to dephosphorylate substrates in vivo. This transient inactivation of PTPs occurs as their conserved catalytic cysteine residue reacts with cellular oxidants thereby abolishing the ability of this reactive cysteine to attack the phosphate of the target substrate. Hence, in vivo, the inhibition of specific PTPs in response to regulated and localized rises in cellular oxidants enables phospho‐dependent signaling. We present assays that measure the endogenous activity of specific PTPs that become transiently inactivated in cells exposed to growth factors. Here, we describe the methods and highlight the pitfalls to avoid post‐lysis oxidation of PTPs in order to assess the inactivation and the reactivation of PTPs targeted by cellular oxidants in signal transduction. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Cell transfection (optional) Support Protocol: Preparation of degassed lysis buffers Basic Protocol 2: Cellular extraction in anaerobic conditions Basic Protocol 3: Enrichment and activity assay of specific PTPs Alternate Protocol: Measurement of active PTPs via direct cysteinyl labeling

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Regulation of PTP1B activation through disruption of redox-complex formation

Cited by 25 publications

References 30 publications

Redox regulation of the insulin signalling pathway

Redox regulation of the insulin signalling pathway

Targeting Reactive Oxygen Species Capacity of Tumor Cells with Repurposed Drug as an Anticancer Therapy

In Vitro Activity Assays to Quantitatively Assess the Endogenous Reversible Oxidation State of Protein Tyrosine Phosphatases in Cells

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