Novel function of DUSP14/MKP6 (dual specific phosphatase 14) as a nonspecific regulatory molecule for delayed-type hypersensitivity

Nakano, Yumiko

doi:10.1111/j.1365-2133.2006.07708.x

Cited by 11 publications

(4 citation statements)

References 30 publications

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“…The production of IL (interleukin)-2 is also enhanced in these T-cells which is consistent with previous findings implicating ERK and JNK in the production of IL-2 [160,161]. It has been suggested that DUSP14 may be the NSF ('non-specific suppressor factor') known to play a role in regulating delayed-type hypersensitivity and contact hypersensitivity by an unknown mechanism [159]. It has been suggested that DUSP14 may be the NSF ('non-specific suppressor factor') known to play a role in regulating delayed-type hypersensitivity and contact hypersensitivity by an unknown mechanism [159].…”

Section: Dusp14supporting

confidence: 90%

Dual-specificity phosphatases: critical regulators with diverse cellular targets

Patterson

Brummer

O'Brien

et al. 2009

Biochemical Journal

652

650

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DUSPs (dual-specificity phosphatases) are a heterogeneous group of protein phosphatases that can dephosphorylate both phosphotyrosine and phosphoserine/phosphothreonine residues within the one substrate. DUSPs have been implicated as major modulators of critical signalling pathways that are dysregulated in various diseases. DUSPs can be divided into six subgroups on the basis of sequence similarity that include slingshots, PRLs (phosphatases of regenerating liver), Cdc14 phosphatases (Cdc is cell division cycle), PTENs (phosphatase and tensin homologues deleted on chromosome 10), myotubularins, MKPs (mitogen-activated protein kinase phosphatases) and atypical DUSPs. Of these subgroups, a great deal of research has focused on the characterization of the MKPs. As their name suggests, MKPs dephosphorylate MAPK (mitogen-activated protein kinase) proteins ERK (extracellular-signal-regulated kinase), JNK (c-Jun N-terminal kinase) and p38 with specificity distinct from that of individual MKP proteins. Atypical DUSPs are mostly of low-molecular-mass and lack the N-terminal CH2 (Cdc25 homology 2) domain common to MKPs. The discovery of most atypical DUSPs has occurred in the last 6 years, which has initiated a large amount of interest in their role and regulation. In the past, atypical DUSPs have generally been grouped together with the MKPs and characterized for their role in MAPK signalling cascades. Indeed, some have been shown to dephosphorylate MAPKs. The current literature hints at the potential of the atypical DUSPs as important signalling regulators, but is crowded with conflicting reports. The present review provides an overview of the DUSP family before focusing on atypical DUSPs, emerging as a group of proteins with vastly diverse substrate specificity and function.

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Section: Dusp14supporting

confidence: 90%

Dual-specificity phosphatases: critical regulators with diverse cellular targets

Patterson

Brummer

O'Brien

et al. 2009

Biochemical Journal

652

650

View full text Add to dashboard Cite

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“…ALP activity was assessed at day 10 using a phosphate assay kit (BioAssay Systems, USA), and the assessment was based on the cleavage of p-nitrophenyl phosphate, as described elsewhere (31). The product of the enzyme reaction, p-nitrophenol, was assessed by measuring the absorbance at 405 nm.…”

Section: Methodsmentioning

confidence: 99%

Serotonin regulates osteoblast proliferation and function in vitro

Dai

Shi

et al. 2014

Braz J Med Biol Res

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The monoamine serotonin (5-hydroxytryptamine, 5-HT), a well-known neurotransmitter, also has important functions outside the central nervous system. The objective of this study was to investigate the role of 5-HT in the proliferation, differentiation, and function of osteoblasts in vitro. We treated rat primary calvarial osteoblasts with various concentrations of 5-HT (1 nM to 10 µM) and assessed the rate of osteoblast proliferation, expression levels of osteoblast-specific proteins and genes, and the ability to form mineralized nodules. Next, we detected which 5-HT receptor subtypes were expressed in rat osteoblasts at different stages of osteoblast differentiation. We found that 5-HT could inhibit osteoblast proliferation, differentiation, and mineralization at low concentrations, but this inhibitory effect was mitigated at relatively high concentrations. Six of the 5-HT receptor subtypes (5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, and 5-HT2C) were found to exist in rat osteoblasts. Of these, 5-HT2A and 5-HT1B receptors had the highest expression levels, at both early and late stages of differentiation. Our results indicated that 5-HT can regulate osteoblast proliferation and function in vitro.

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“…The buried surface area at the interface of the two molecules is only 209 Å 2 , which suggests that the monomer is likely to be the biologically relevant unit. A previous report by Nakano indicated that DUSP14 exists as a mixture of monomers and dimers in solution under nonreducing conditions, but is driven toward the monomeric state under reducing conditions (Nakano, 2007). All but one of the Cys residues in DUSP14 are buried from the solvent and Cys133, the only exposed Cys residue, is not located near any other symmetry-related Cys residue.…”

Section: Resultsmentioning

confidence: 90%

“…DUSP14 contributes to the regulation of CD28 signaling by interacting with the cytoplasmic tail of CD28, thereby co-localizing DUSP14 with recently activated MAP kinases at the plasma membrane and facilitating their deactivation prior to nuclear translocation. A report by Nakano also identified DUSP14 as a nonspecific regulatory molecule for delayed-type hypersensitivity, indicating that DUSP14 may itself have some utility as a therapeutic agent (Nakano, 2007). DUSP14 has also been shown to contribute to the proliferation of pancreatic -cells by affecting ERK activity, which raises further questions as to the possible roles of DUSP14 in cellular growth, proliferation and differentiation in other cell types such as cancer (Klinger et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Overproduction, purification and structure determination of human dual-specificity phosphatase 14

Lountos

Tropea

Cherry

et al. 2009

Acta Crystallogr D Biol Cryst

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Dual-specificity phosphatases (DUSPs) are enzymes that participate in the regulation of biological processes such as cell growth, differentiation, transcription and metabolism. A number of DUSPs are able to dephosphorylate phosphorylated serine, threonine and tyrosine residues on mitogen-activated protein kinases (MAPKs) and thus are also classified as MAPK phosphatases (MKPs). As an increasing number of DUSPs are being identified and characterized, there is a growing need to understand their biological activities at the molecular level. There is also significant interest in identifying DUSPs that could be potential targets for drugs that modulate MAPK-dependent signaling and immune responses, which have been implicated in a variety of maladies including cancer, infectious diseases and inflammatory disorders. Here, the overproduction, purification and crystal structure at 1.88 A resolution of human dual-specificity phosphatase 14, DUSP14 (MKP6), are reported. This structural information should accelerate the study of DUSP14 at the molecular level and may also accelerate the discovery and development of novel therapeutic agents.

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Novel function of DUSP14/MKP6 (dual specific phosphatase 14) as a nonspecific regulatory molecule for delayed-type hypersensitivity

Abstract: These studies indicate for the first time that NSF is a dimer of DUSP14 secreted by macrophage-like suppressor cells by stimulation with hapten-conjugated cells and exerts a regulatory function on CHS through DCs as a secreted phosphatase.

Cited by 11 publications

References 30 publications

Dual-specificity phosphatases: critical regulators with diverse cellular targets

Dual-specificity phosphatases: critical regulators with diverse cellular targets

Serotonin regulates osteoblast proliferation and function in vitro

Overproduction, purification and structure determination of human dual-specificity phosphatase 14

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