Dual-Specificity Phosphatases as Molecular Targets for Inhibition in Human Disease

2014 ◽  
Vol 20 (14) ◽  
pp. 2251-2273 ◽  
Author(s):  
Pablo Ríos ◽  
Caroline E. Nunes-Xavier ◽  
Lydia Tabernero ◽  
Maja Köhn ◽  
Rafael Pulido
Keyword(s):  
Human Disease ◽  
Molecular Targets ◽  
Dual Specificity ◽  
Dual Specificity Phosphatases

scholarly journals Dual Specificity Phosphatases: From Molecular Mechanisms to Biological Function

2019 ◽  
Vol 20 (18) ◽  
pp. 4372 ◽  
Author(s):  
Rafael Pulido ◽  
Roland Lang
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Human Disease ◽  
Molecular Mechanisms ◽  
Biological Function ◽  
Tyrosine Phosphatase ◽  
Heterogeneous Group ◽  
Class I ◽  
Protein Tyrosine ◽  
Dual Specificity ◽  
Dual Specificity Phosphatases

Dual specificity phosphatases (DUSPs) constitute a heterogeneous group of enzymes, relevant in human disease, which belong to the class I Cys-based group of protein tyrosine phosphatase (PTP) gene superfamily [...]

scholarly journals A Review of DUSP26: Structure, Regulation and Relevance in Human Disease

2021 ◽  
Vol 22 (2) ◽  
pp. 776
Author(s):  
Elliott M. Thompson ◽  
Andrew W. Stoker
Keyword(s):  
Human Disease ◽  
Physiological Role ◽  
Crystallographic Structure ◽  
Physiological Processes ◽  
Intracellular Signalling Pathways ◽  
Binding Partners ◽  
Mapk Cascades ◽  
Dual Specificity ◽  
Dual Specificity Phosphatases ◽  
Key Pathways

Dual specificity phosphatases (DUSPs) play a crucial role in the regulation of intracellular signalling pathways, which in turn influence a broad range of physiological processes. DUSP malfunction is increasingly observed in a broad range of human diseases due to deregulation of key pathways, most notably the MAP kinase (MAPK) cascades. Dual specificity phosphatase 26 (DUSP26) is an atypical DUSP with a range of physiological substrates including the MAPKs. The residues that govern DUSP26 substrate specificity are yet to be determined; however, recent evidence suggests that interactions with a binding partner may be required for DUSP26 catalytic activity. DUSP26 is heavily implicated in cancer where, akin to other DUSPs, it displays both tumour-suppressive and -promoting properties, depending on the context. Here we review DUSP26 by evaluating its transcriptional patterns, protein crystallographic structure and substrate binding, as well as its physiological role(s) and binding partners, its role in human disease and the development of DUSP26 inhibitors.

scholarly journals Dual-Specificity, Tyrosine Phosphorylation-Regulated Kinases (DYRKs) and cdc2-Like Kinases (CLKs) in Human Disease, an Overview

2021 ◽  
Vol 22 (11) ◽  
pp. 6047
Author(s):  
Mattias F. Lindberg ◽  
Laurent Meijer
Keyword(s):  
Tyrosine Phosphorylation ◽  
Human Disease ◽  
Intracellular Signaling ◽  
Neuronal Development ◽  
Viral Infections ◽  
Current Knowledge ◽  
Lymphoblastic Leukemia ◽  
Cell Cycle Control ◽  
Megakaryoblastic Leukemia ◽  
Dual Specificity

Dual-specificity tyrosine phosphorylation-regulated kinases (DYRK1A, 1B, 2-4) and cdc2-like kinases (CLK1-4) belong to the CMGC group of serine/threonine kinases. These protein kinases are involved in multiple cellular functions, including intracellular signaling, mRNA splicing, chromatin transcription, DNA damage repair, cell survival, cell cycle control, differentiation, homocysteine/methionine/folate regulation, body temperature regulation, endocytosis, neuronal development, synaptic plasticity, etc. Abnormal expression and/or activity of some of these kinases, DYRK1A in particular, is seen in many human nervous system diseases, such as cognitive deficits associated with Down syndrome, Alzheimer’s disease and related diseases, tauopathies, dementia, Pick’s disease, Parkinson’s disease and other neurodegenerative diseases, Phelan-McDermid syndrome, autism, and CDKL5 deficiency disorder. DYRKs and CLKs are also involved in diabetes, abnormal folate/methionine metabolism, osteoarthritis, several solid cancers (glioblastoma, breast, and pancreatic cancers) and leukemias (acute lymphoblastic leukemia, acute megakaryoblastic leukemia), viral infections (influenza, HIV-1, HCMV, HCV, CMV, HPV), as well as infections caused by unicellular parasites (Leishmania, Trypanosoma, Plasmodium). This variety of pathological implications calls for (1) a better understanding of the regulations and substrates of DYRKs and CLKs and (2) the development of potent and selective inhibitors of these kinases and their evaluation as therapeutic drugs. This article briefly reviews the current knowledge about DYRK/CLK kinases and their implications in human disease.

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
Sign in / Sign up

Export Citation Format

Share Document