scholarly journals Dual specificity phosphatases 10 and 16 are positive regulators of EGF-stimulated ERK activity: Indirect regulation of ERK signals by JNK/p38 selective MAPK phosphatases

2012 ◽  
Vol 24 (5) ◽  
pp. 1002-1011 ◽  
Author(s):  
Ann R. Finch ◽  
Christopher J. Caunt ◽  
Rebecca M. Perrett ◽  
Krasimira Tsaneva-Atanasova ◽  
Craig A. McArdle
Keyword(s):  
Dual Specificity ◽  
Positive Regulators ◽  
Mapk Phosphatases ◽  
Dual Specificity Phosphatases ◽  
Erk Activity

scholarly journals Dual-Specificity Phosphatases in Neuroblastoma Cell Growth and Differentiation

2019 ◽  
Vol 20 (5) ◽  
pp. 1170 ◽  
Author(s):  
Caroline Nunes-Xavier ◽  
Laura Zaldumbide ◽  
Olaia Aurtenetxe ◽  
Ricardo López-Almaraz ◽  
José López ◽  
...  
Keyword(s):  
Cell Growth ◽  
Map Kinases ◽  
Current Knowledge ◽  
Neuroblastoma Cell ◽  
Neuronal Cell ◽  
Predictive Biomarkers ◽  
Dual Specificity ◽  
Mapk Phosphatases ◽  
Cell Growth And Differentiation ◽  
Dual Specificity Phosphatases

Dual-specificity phosphatases (DUSPs) are important regulators of neuronal cell growth and differentiation by targeting proteins essential to neuronal survival in signaling pathways, among which the MAP kinases (MAPKs) stand out. DUSPs include the MAPK phosphatases (MKPs), a family of enzymes that directly dephosphorylate MAPKs, as well as the small-size atypical DUSPs, a group of low molecular-weight enzymes which display more heterogeneous substrate specificity. Neuroblastoma (NB) is a malignancy intimately associated with the course of neuronal and neuroendocrine cell differentiation, and constitutes the source of more common extracranial solid pediatric tumors. Here, we review the current knowledge on the involvement of MKPs and small-size atypical DUSPs in NB cell growth and differentiation, and discuss the potential of DUSPs as predictive biomarkers and therapeutic targets in human NB.

scholarly journals Gonadotropin-Releasing Hormone and Protein Kinase C Signaling to ERK: Spatiotemporal Regulation of ERK by Docking Domains and Dual-Specificity Phosphatases

2009 ◽  
Vol 23 (4) ◽  
pp. 510-519 ◽  
Author(s):  
Stephen Paul Armstrong ◽  
Christopher James Caunt ◽  
Craig Alexander McArdle
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phorbol Ester ◽  
Fluorescent Protein ◽  
Erk Activation ◽  
Kinase C ◽  
Dual Specificity ◽  
Mapk Phosphatases ◽  
Dual Specificity Phosphatases ◽  
Green Fluorescent

Abstract Activated ERK translocates to the nucleus to regulate transcription. Spatiotemporal aspects of this response dictate biological consequences and are influenced by dual-specificity phosphatases (DUSPs) that can scaffold and dephosphorylate ERK. In HeLa cells, GnRH causes transient and protein kinase C (PKC)-dependent ERK activation, but termination mechanisms are unknown. We now explore DUSP roles using short inhibitory RNA to knock down endogenous ERK, adenoviruses to express GnRH receptors and add-back ERK2-GFP, and automated microscopy to monitor ERK location and activation. GnRH caused rapid and transient increases in dual phosphorylated ERK2 (ppERK2) and nuclear to cytoplasmic ERK2-green fluorescent protein (GFP) ratio, whereas responses to a PKC-activating phorbol ester were more sustained. In cells expressing D319N ERK2-GFP (D319N mutation impairs docking-domain-dependent binding to DUSPs), GnRH caused more sustained increases in ppERK2 and nuclear to cytoplasmic ERK2-GFP ratio and also had more pronounced effects on Egr-1 luciferase (a transcriptional reporter for ERK activation). Cycloheximide caused more sustained effects of GnRH and phorbol ester on ppERK, suggesting termination by nuclear-inducible DUSPs. GnRH also increased expression of nuclear-inducible DUSP1 and -4, but their knockdown did not alter GnRH-mediated ERK signaling. Screening a short inhibitory RNA library targeting 16 DUSPs (nuclear-inducible DUSPs, cytoplasmic ERK MAPK phosphatases, c-Jun N-terminal kinase/p38 MAPK phosphatases, and atypical DUSPs) revealed GnRH effects to be influenced by DUSPs 5, 9, 10, 16, and 3 (i.e. by each DUSP class). Thus, GnRH-mediated ERK responses (like PKC-mediated ERK responses) are dependent on protein neosynthesis and docking-domain-dependent binding, but for GnRH activation (unlike PKC activation), this does not reflect dependence on nuclear-inducible DUSPs. Termination of these GnRH effects is apparently dependent upon a preexisting rapid turnover protein.

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.

scholarly journals Dual-specificity phosphatases in mental and neurological disorders

2020 ◽  
pp. 101906
Author(s):  
Ning An ◽  
Katherine Bassil ◽  
Ghazi I. Al Jowf ◽  
Harry W.M. Steinbusch ◽  
Markus Rothermel ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Dual Specificity ◽  
Dual Specificity Phosphatases

scholarly journals Regulation of Dual-specificity Phosphatases M3/6 and hVH5 by Phorbol Esters

2000 ◽  
Vol 275 (41) ◽  
pp. 31755-31762 ◽  
Author(s):  
Thomas R. Johnson ◽  
Joseph R. Biggs ◽  
Sarah E. Winbourn ◽  
Andrew S. Kraft
Keyword(s):  
Phorbol Esters ◽  
Dual Specificity ◽  
Dual Specificity Phosphatases
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