scholarly journals Dual specificity phosphatase 22 relates to skin lesion degree and biologics history, while its longitudinal elevation during treatment reflects better outcome in psoriasis patients

2021 ◽  
Author(s):  
Cailing E ◽  
Yong Fang ◽  
Shixing Wu ◽  
Zudong Meng ◽  
Guifang Qin ◽  
...  
Keyword(s):  
Skin Lesion ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity

scholarly journals Structural analysis of human dual-specificity phosphatase 22 complexed with a phosphotyrosine-like substrate

2015 ◽  
Vol 71 (2) ◽  
pp. 199-205 ◽  
Author(s):  
George T. Lountos ◽  
Scott Cherry ◽  
Joseph E. Tropea ◽  
David S. Waugh
Keyword(s):  
Crystal Structure ◽  
Structural Analysis ◽  
Phosphatase Activity ◽  
Small Molecule ◽  
Molecular Basis ◽  
Protein Tyrosine Phosphatases ◽  
Simple Method ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity ◽  
Nitrophenyl Phosphate

4-Nitrophenyl phosphate (p-nitrophenyl phosphate, pNPP) is widely used as a small molecule phosphotyrosine-like substrate in activity assays for protein tyrosine phosphatases. It is a colorless substrate that upon hydrolysis is converted to a yellow 4-nitrophenolate ion that can be monitored by absorbance at 405 nm. Therefore, the pNPP assay has been widely adopted as a quick and simple method to assess phosphatase activity and is also commonly used in assays to screen for inhibitors. Here, the first crystal structure is presented of a dual-specificity phosphatase, human dual-specificity phosphatase 22 (DUSP22), in complex with pNPP. The structure illuminates the molecular basis for substrate binding and may also facilitate the structure-assisted development of DUSP22 inhibitors.

scholarly journals Dual Specificity Phosphatase 6 Protects Neural Stem Cells from β-Amyloid-Induced Cytotoxicity through ERK1/2 Inactivation

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 181 ◽  
Author(s):  
Wang Liao ◽  
Yuqiu Zheng ◽  
Wenli Fang ◽  
Shaowei Liao ◽  
Ying Xiong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Neural Stem Cells ◽  
Western Blot ◽  
Mitochondrial Dysfunction ◽  
Neuroprotective Effect ◽  
Dependent Manner ◽  
Dual Specificity Phosphatase ◽  
Cell Vitality ◽  
Dual Specificity

Alzheimer’s disease (AD) is a devastating neurodegenerative disease with limited treatment options and no cure. Beta-amyloid (Aβ) is a hallmark of AD that has potent neurotoxicity in neural stem cells (NSCs). Dual specificity phosphatase 6 (DUSP6) is a member of the mitogen-activated protein kinases (MAPKs), which is involved in regulating various physiological and pathological processes. Whether DUSP6 has a protective effect on Aβ-induced NSC injury remains to be explored. C17.2 neural stem cells were transfected with DUSP6-overexpressed plasmid. NSCs with or without DUSP6 overexpression were administrated with Aβ25–35 at various concentrations (i.e., 0, 2.5, 5 μM). DUSP6 expression after Aβ treatment was detected by Real-Time Polymerase Chain Reaction (RT-PCR) and Western blot and cell vitality was examined by the CCK8 assay. The oxidative stress (intracellular reactive oxygen species (ROS) and malondialdehyde (MDA)), endoplasmic reticulum stress (ER calcium level) and mitochondrial dysfunction (cytochrome c homeostasis) were tested. The expression of p-ERK1/2 and ERK1/2 were assayed by Western blot. Our results showed that Aβ decreased the expression of DUSP6 in a dose-dependent manner. The overexpression of DUSP6 increased the cell vitality of NSCs after Aβ treatment. Oxidative stress, ER stress, and mitochondrial dysfunction induced by Aβ could be restored by DUSP6 overexpression. Additionally, the Aβ-induced ERK1/2 activation was reversed. In summary, DUSP6 might have a neuroprotective effect on Aβ-induced cytotoxicity, probably via ERK1/2 activation.

scholarly journals Dual specificity phosphatase 15 regulates Erk activation in Schwann cells

2017 ◽  
Vol 140 (3) ◽  
pp. 368-382 ◽  
Author(s):  
José F. Rodríguez-Molina ◽  
Camila Lopez-Anido ◽  
Ki H. Ma ◽  
Chongyu Zhang ◽  
Tyler Olson ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Erk Activation ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity

scholarly journals Structure of human dual-specificity phosphatase 7, a potential cancer drug target

2015 ◽  
Vol 71 (6) ◽  
pp. 650-656 ◽  
Author(s):  
George T. Lountos ◽  
Brian P. Austin ◽  
Joseph E. Tropea ◽  
David S. Waugh
Keyword(s):  
Catalytic Domain ◽  
Three Dimensional ◽  
Mitogen Activated Protein Kinase ◽  
Cancer Drug ◽  
Dual Specificity Phosphatase ◽  
Dual Specificity ◽  
Starting Point ◽  
Mitogen Activated Protein ◽  
Dual Specificity Phosphatases

Human dual-specificity phosphatase 7 (DUSP7/Pyst2) is a 320-residue protein that belongs to the mitogen-activated protein kinase phosphatase (MKP) subfamily of dual-specificity phosphatases. Although its precise biological function is still not fully understood, previous reports have demonstrated that DUSP7 is overexpressed in myeloid leukemia and other malignancies. Therefore, there is interest in developing DUSP7 inhibitors as potential therapeutic agents, especially for cancer. Here, the purification, crystallization and structure determination of the catalytic domain of DUSP7 (Ser141–Ser289/C232S) at 1.67 Å resolution are reported. The structure described here provides a starting point for structure-assisted inhibitor-design efforts and adds to the growing knowledge base of three-dimensional structures of the dual-specificity phosphatase family.

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