Dual-specificity phosphatases 2: surprising positive effect at the molecular level and a potential biomarker of diseases

Wei, Wenyi; Jiao, Yan; Postlethwaite, Arnold E.; Stuart, Joshua M.; Wang, Y.; Sun, Di; Gu, Weikuan

doi:10.1038/gene.2012.54

Cited by 46 publications

(36 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, when we examined the 25 genes whose expression was most upregulated by exercise (ranging from 19.6 to 2.3 fold increase) we found from literature searches that 13 of the genes have been associated with pro-inflammatory activation. Among them, for example, DUSP2 worsens inflammatory diseases like arthritis (Wei, Jiao, Postlethwaite, Stuart, Wang, Sun, and Gu, 2013), HSP70 promotes atherosclerosis (Yadav, Kumar, and Jha, 2013), and PDE4B plays a role in autoimmune inflammatory diseases like systemic lupus erythematosus (Yougbare, Boire, Roy, Lugnier, and Rouseau, 2013). Six of the 25 genes were clearly associated with anti-inflammatory functions, and the remaining six had not been linked previously with either pro- or antiinflammatory activity.…”

Section: Discussionmentioning

confidence: 99%

Impact of brief exercise on circulating monocyte gene and microRNA expression: Implications for atherosclerotic vascular disease

Radom‐Aizik

Zaldivar

Haddad

et al. 2014

Brain, Behavior, and Immunity

View full text Add to dashboard Cite

Physical activity can prevent and/or attenuate atherosclerosis, a disease clearly linked to inflammation. Paradoxically, even brief exercise induces a stress response and increases inflammatory cells like monocytes in the circulation. We hypothesized that exercise would regulate the expression of genes, gene pathways, and microRNAs in monocytes in a way that could limit pro-inflammatory function and drive monocytes to prevent, rather than contribute to, atherosclerosis. Twelve healthy men (22-30 yr old) performed ten 2-min bouts of cycle ergometer exercise at a constant work equivalent to an average of 82% of maximum O2 consumption interspersed with 1-min rest. Blood was drawn before and immediately after the exercise. Monocytes were isolated from peripheral blood mononuclear cells. Flow cytometry was used to identify monocyte subtypes. We used Affymetrix U133+2.0 arrays for gene expression and Agilent Human miRNA V2 Microarray for miRNAs. A stringent statistical approach (FDR < 0.05) was used to determine that exercise significantly altered the expression of 894 annotated genes and 19 miRNAs. We found distinct gene alterations that were likely to direct monocytes in an anti-inflammatory, anti-atherogenic pathway, including the downregulation of monocyte TNF, TLR4, and CD36 genes and the upregulation of EREG and CXCR4. Exercise significantly altered a number of microRNAs that likely influence monocytes involvement in vascular health. Exercise leads to a novel genomic profile of circulating monocytes, which appears to promote cardiovascular health despite the overall stress response.

show abstract

Section: Discussionmentioning

confidence: 99%

Impact of brief exercise on circulating monocyte gene and microRNA expression: Implications for atherosclerotic vascular disease

Radom‐Aizik

Zaldivar

Haddad

et al. 2014

Brain, Behavior, and Immunity

View full text Add to dashboard Cite

show abstract

“…Not only do the DUSPs have a dephosphorylating capacity, but they also function to anchor or shuttle MAPKs and thus control their subcellular localization (Masuda et al, 2001;Karlsson et al, 2004). Analysis of the human genome revealed 30 putative DUSP genes (Wei et al, 2013), 11 of which are specific for MAPKs, ERK, JNK and p38. Nineteen of these genes have been referred to as 'atypical' DUSPs (Saxena and Mustelin, 2000;Alonso et al, 2004).…”

Section: Dusps and Cancermentioning

confidence: 99%

Targeting DUSPs in glioblastomas – wielding a double‐edged sword?

Prabhakar

Asuthkar

Lee

et al. 2013

Cell Biology International

View full text Add to dashboard Cite

Several dual-specificity phosphatases (DUSPs) that play key roles in the direct or indirect inactivation of different MAP kinases (MAPKs) have been implicated in human cancers over the past decade. This has led to a growing interest in identifying DUSPs and their specific inhibitors for further testing and validation as therapeutic targets in human cancers. However, the lack of understanding of the complex regulatory mechanisms and cross-talks between MAPK signaling pathways, combined with the fact that DUSPs can act as a double-edged sword in cancer progression, calls for a more careful and thorough investigation. Among the various types of brain cancer, glioblastoma multiforme (GBM) is notorious for its aggressiveness and resistance to current treatment modalities. This has led to the search for new molecular targets, particularly those involving various signaling pathways. DUSPs appear to be a promising target, but much more information on DUSP targets and their effects on GBM is needed before potential therapies can be developed, tested, and validated. This review identifies and summarize the specific roles of DUSP1, DUSP4, DUSP6 and DUSP26 that have been implicated in GBM.

show abstract

“…CCL3L3 is a ligand for CCR1, CCR3 and CCR5 , known to be chemotactic for monocytes and lymphocytes (18). DUSP1 and DUSP2 are dual specificity phosphatases; DUSP2 dephosphorylates STAT3 , leading to inhibition of survival and proliferation signals (19–21), and an age-associated decrease in DUSP1 function contributed to inappropriate IL-10 production in monocytes before and after influenza vaccination (22). To determine whether downregulation of these three genes was a result of changes in cell subset composition or observed in subpopulations of cells, we performed transcriptional profiling on sorted B and T cells in a subset of individuals from three seasons.…”

Section: Resultsmentioning

confidence: 99%

Seasonal Variability and Shared Molecular Signatures of Inactivated Influenza Vaccination in Young and Older Adults

Avey

Mohanty

Chawla

et al. 2019

Preprint

View full text Add to dashboard Cite

23The seasonal influenza vaccine is an important public health tool but is only effective in a subset of 24individuals. The identification of molecular signatures provides a mechanism to understand the drivers of 25 vaccine-induced immunity. Most previously reported molecular signatures of influenza vaccination were 26derived from a single age group or season, ignoring the effects of immunosenescence or vaccine 27 composition. Thus, it remains unclear how immune signatures of vaccine response change with age across 28 multiple seasons. Here we profile the transcriptional landscape of young and older adults over five 29consecutive vaccination seasons to identify shared signatures of vaccine response as well as marked 30 seasonal differences. Along with substantial variability in vaccine-induced signatures across seasons, we 31 uncovered a common transcriptional signature 28 days post-vaccination in both young and older adults. 32However, gene expression patterns associated with vaccine-induced antibody responses were distinct in 33 young and older adults; for example, increased expression of Killer Cell Lectin Like Receptor B1 (KLRB1; 34 CD161) 28 days post-vaccination positively and negatively predicted vaccine-induced antibody responses 35in young and older adults, respectively. These findings contribute new insights for developing more 36 effective influenza vaccines, particularly in older adults. 37 38 Keywords 39 systems vaccinology; seasonal variability; influenza; vaccination; aging; transcriptional profiling 40 41 42

show abstract

Dual-specificity phosphatases 2: surprising positive effect at the molecular level and a potential biomarker of diseases

Cited by 46 publications

References 66 publications

Impact of brief exercise on circulating monocyte gene and microRNA expression: Implications for atherosclerotic vascular disease

Impact of brief exercise on circulating monocyte gene and microRNA expression: Implications for atherosclerotic vascular disease

Targeting DUSPs in glioblastomas – wielding a double‐edged sword?

Seasonal Variability and Shared Molecular Signatures of Inactivated Influenza Vaccination in Young and Older Adults

Contact Info

Product

Resources

About