Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Christophe Grosset
 + 1608 word(s) 1608 2021-11-03 11:06:57 |
2 The format is correct
Lindsay Dong
+ 596 word(s) 2204 2021-11-05 06:36:37 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Grosset, C. Dual-Specificity Phosphatase 9 (DUSP9). Encyclopedia. Available online: https://encyclopedia.pub/entry/15727 (accessed on 27 July 2024).
Grosset C. Dual-Specificity Phosphatase 9 (DUSP9). Encyclopedia. Available at: https://encyclopedia.pub/entry/15727. Accessed July 27, 2024.
Grosset, Christophe. "Dual-Specificity Phosphatase 9 (DUSP9)" Encyclopedia, https://encyclopedia.pub/entry/15727 (accessed July 27, 2024).
Grosset, C. (2021, November 04). Dual-Specificity Phosphatase 9 (DUSP9). In Encyclopedia. https://encyclopedia.pub/entry/15727
Grosset, Christophe. "Dual-Specificity Phosphatase 9 (DUSP9)." Encyclopedia. Web. 04 November, 2021.
Dual-Specificity Phosphatase 9 (DUSP9)
Edit
This entry is adapted from the peer-reviewed paper 10.3390/ijms222111538

Dual-specificity phosphatase 9 (DUSP9) belongs to the threonine/tyrosine dual-specific phosphatase family and was first described in 1997, is known to dephosphorylate ERK1/2, p38, JNK and ASK1, and thereby to control various MAPK pathway cascades. As a consequence, DUSP9 plays a major role in human pathologies and more specifically in cardiac dysfunction, liver metabolic syndromes, diabetes, obesity and cancer including drug response and cell stemness. 

mitogen-activated protein kinase dual-specificity phosphatase MAP kinase phosphatase

1. Introduction 

The mitogen-activated protein kinase (MAPK) signaling pathways are crucial in cell function and homeostasis. MAPKs regulate pathophysiological processes by controlling signal translation and cellular response such as survival, proliferation, differentiation and migration [1][2][3]. They are activated by a double phosphorylation process on tyrosine and threonine residues in a conserved Thr-X-Tyr motif (X being any amino acid) [4][5]. Activation of MAPK pathways triggers multiple intracellular signaling cascades. Each cascade is initiated by a specific signal and leads to the activation of a particular MAPK [6]. Once activated, MAPK can phosphorylate various cytoplasmic and/or nuclear substrates and induce changes in the function of target proteins and gene expression [6]. Spatial localization of MAPKs also determines the target substrates and subsequent cellular effects [7].

Phosphatases reverse phosphorylation and return MAPKs to an inactive state. The dual specificity phosphatase (DUSP) family belongs to the 199 phosphatases encoded in the human genome. This family is composed of 61 phosphatases capable of downregulating MAPKs by dephosphorylating both tyrosine and serine/threonine residues in a single substrate [8][9]. The phosphorylation of proteins is a reversible process. This prevents the abnormal activation of the signal and fine-tunes its activity and downstream effects [3][8]. The balance between phosphorylation and dephosphorylation controls the expression, function, activity and localization of many proteins [8][10]. Dephosphorylation by DUSPs regulates the duration, intensity and spatiotemporal profile of the MAPK signaling cascade [11]. This dephosphorylation takes place thanks to the highly conserved phosphatase site which contains arginine, cysteine and aspartic acid [3][8][12]. In addition to the active site common to all DUSPs, some DUSPs contain a MAP kinase-binding motif (MKB), also called a kinase-interacting motif (KIM), which interacts with the common docking domain of MAPKs to allow the interaction between the enzyme and the substrate [3][8][12][13]. Ten DUSPs containing the KIM domain are classified as typical DUSPs or MAP kinase phosphatases (MKPs) (Table 1), while those which do not have this domain (16 phosphatases in total) are called atypical DUSPs [3][5][14]. However, there are a few exceptions. DUSP2, DUSP5 and DUSP8 are typical DUSPs and contain the KIM domain but they are not called MKPs. On the other hand, DUSP14 and DUSP26, which are atypical DUSPs and do not contain a KIM domain, are called MKP6 and MKP8, respectively (Table 1) [3][14]. Typical DUSPs are the best characterized within the DUSP family [14] and this comprises the typical DUSP named DUSP9 or MKP4, which was first described in 1997 by Muda and collaborators [12]. This 42-kDa protein dephosphorylates several substrates including JNK, p38, the MAPKKK apoptosis signal-regulating kinase 1 (ASK1) and ERK1/2 with a high specificity for ERK kinases [3][12].

Table 1. General information and main functions of MAP kinase phosphatases (MKP).
Classification Gene Symbol Synonyms Chromosomal Localization Cell Localization MAPK Substrates (Others) Inducible by MAPKs Main Functions in Physiological and Pathophysiological States
Typical MKPs DUSP1 MKP1 5 Nuclear JNK, p38 > ERK ERK, p38 Involved in infectious diseases, pulmonary diseases, inflammatory disorders, atherosclerosis, tumorigenesis and tumor progression [15].
DUSP2 PAC1 2 Nuclear ERK, JNK, p38 ERK, JNK Involved in immune and inflammatory responses, cancer, CLN3 disease and endometriosis [16].
DUSP4 MKP2 8 Nuclear ERK, JNK > p38 ERK Involved in inflammatory cytokine secretion, susceptibility to sepsis shock, and resistance to Leishmania mexicana infection [17][18].
DUSP5 hVH3 10 Nuclear ERK ERK Plays an anti-inflammatory role and has tumor suppressive functions in several types of cancer [19].
DUSP6 MKP3 12 Cytoplasmic ERK ERK Plays a role in carcinogenesis in several cancers as an oncogene or a tumor suppressor [20].
DUSP7 MKPX 3 Cytoplasmic ERK, JNK, p38 N/D Involved in some cancers [21].
DUSP8 hVH5 11 Dually-located ERK, JNK, p38 N/D Plays a role in the central nervous system, circulatory system, urinary system, immune system, genetic diseases and cancers [22].
DUSP9 MKP4 X Cytoplasmic ERK >> p38, JNK N/D Involved in development of cardiac dystrophy, metabolic diseases and cancers [23][24][25][26][27].
(MAP3K5/ASK1)
DUSP10 MKP5 1 Dually-located JNK, p38 >> ERK N/D Involved in immune response, anti-inflammatory response and some cancers [28].
DUSP16 MKP7 12 Dually-located JNK N/D Involved in non-alcoholic steatohepatitis and some cancers [29].
Atypical MKPs DUSP14 MKP6 17 Dually-located ERK, JNK, p38 N/D Involved in immune response, bone diseases and cancers [30].
DUSP26 MKP8 8 Nuclear p38 N/D Regulates neuronal cell proliferation and acts as an oncogene or a tumor suppressor depending on the cellular context [31].
Data were also extracted from the following publications: [3][32][33][10][34][35][36][37]. N/D: not determinate.

2. General Characteristics of DUSP9 and Mechanisms of Regulation

DUSP9 is a typical DUSP characterized by the presence of an MKB/KIM motif and a phosphatase domain, which shares structural homology with other DUSPs [8]. Sequence homology analysis of DUSP9 showed 61% identity with DUSP22/MKP-X, 57% with DUSP6/MKP-3 and 35% with DUSP8 [12]. DUSP9 contains a C-terminal catalytic domain common to all DUSPs. The core of this domain, which consists in residues of arginine, cysteine and aspartic acid (Figure 1), is highly conserved and carries the phosphatase activity [32][12][13][38]. Arginine at position 296 forms hydrogen bonds with a phosphate group on the substrate and stabilizes the transition state. Cysteine at position 290 functions as an active nucleophile site forming a covalent thiol-phosphate intermediate, while aspartic acid in position 259 acts as a catalytic acid to give a proton to the leaving group (Figure 1) [12][38][39].
Ijms 22 11538 g001 550
Figure 1. Structure of the phosphatase active site of DUSP9. (A) Crystallographic representation of the phosphatase site of DUSP9 with a focus on its catalytic part (see region of interest in red box) composed of a cysteine at position 290, an arginine at position 296 and an aspartic acid at position 259 (from RCSB Protein Data Bank: https://www.rcsb.org/3d-view/3LJ8, accessed on 1 September 2021) [40]. (B) Higher magnification of region of interest shown in panel A. (C) Same image than in Panel B with inserted substrates and molecular interactions between the three amino acyls and substrate.
The MKB/KIM motif is composed of two CDC25 homology domains and an intermediate group of basic amino acids mediating the interaction with the common domain of MAPKs [10][12][13][39]. DUSP9 is able to undergo a conformational rearrangement allowing it to alternate between a partially active structure and a fully active structure [38]. A crystallographic representation of the catalytic site of DUSP9 showed a unique structure with significant differences between the catalytic core and several surrounding loops compared to other MKPs. The catalytic site of DUSP9 deviates considerably from the canonical conformation of DUSPs, which may explain the low catalytic activity of this protein in the absence of specific substrates [13][38]. The DUSP9 protein alone has very low catalytic activity but binding to MAPK through the MKB/KIM domain significantly increases its phosphatase activity [12][13]. The binding of the substrate likely triggers a conformational change and thus increases its catalytic efficiency [13][38]. DUSP9 is capable of binding and being activated by different MAPKs. Measurements in the presence of para-nitrophenylphosphate (pNPP) showed DUSP9 binding preference and activation by ERK2, JNK and p38 MAPK [13][27][39].
At a functional level, DUSP9 phosphatase is unique. It plays an important role in the dephosphorylation and inactivation of specific kinases such as ASK1, ERK1/2, p38 and JNK (Figure 2). This results in a negative control of MAPK signal transduction and a fine tuning of their duration and intensity [9][11][25]. The endogenous catalytic activity of DUSP9 was studied for the first time by Muda and collaborators by measuring the hydrolysis of pNPP in the presence of increasing doses of a purified human recombinant protein. DUSP9 displayed a dose-dependent catalytic activity which was directly proportional to the amount of protein added [12]. The DUSP9 protein has a broad specificity for MAPK substrates. It can dephosphorylate ERK-family MAPKs, stress-activated JNK and p38 MAPKs (Figure 2), but its effect is significantly higher and more specific for ERK kinases [12][38]. In hepatic tumor cells, DUSP9 negatively regulates the RAS/RAF/MEK/ERK signal by dephosphorylating ERK1/ERK2 and a low level of DUSP9 is correlated with an elevated level of phospho-ERK1/2 in hepatocellular carcinoma (HCC) samples [9]. Co-incubation of ERK2 with increasing concentrations of DUSP9 results in the dose-dependent blockade of ERK2 target phosphorylation such as stathmin [12]. This catalytic activity is effectively inhibited by sodium vanadate, which is an inhibitor of protein tyrosine phosphatases [12].
Ijms 22 11538 g002 550
Figure 2. Regulation of DUSP9 expression and connection with MAPK pathways. Following the activation of tyrosine kinase receptors (TKR), MAPK pathways are activated through the successive phosphorylations of MAPKKKs (among which ASK1), MAPKKs MKK3/6, MKK4/7 and MEK1/2, and MAPKs p38, JNK and ERK. Phosphorylated MAPKs translocate to the nucleus and induce expression of the downstream targets c-FOS, ERG1, NANOG and HIF1, among others. In murine embryonic stem cells, the binding of BMP4 on its receptor induces the phosphorylation of Smad1/5, which then associates with Smad4. The Smad1/5–Smad4 complex translocates to the nucleus, binds the DUSP9 promoter and induces its transcriptional expression. Transcription factors HIF1-α and ETS can also induce DUSP9 expression. Besides the BMP signal, mTOR, RAR-α and ERβ pathways can also potentiate the transcription of the DUSP9 gene. Following NANOG binding on LINCU promoter, the long non-coding RNA LincU is transcribed and exported in the cytoplasm where it associates with DUSP9 and stabilizes it. Stable DUSP9 can dephosphorylate its substrates, including ERK1/2, p38, JNK and ASK1. In the absence of LincU RNA, DUSP9 protein is unstable and is polyubiquitinylated before its degradation by the proteasome. DUSP9 can also be post-transcriptionally regulated by miR-212 and miR-1246, which target the 3′-untranslated region of its mRNA. In summary, DUSP9 expression is tightly regulated by transcriptional, post-transcriptional and post-translational mechanisms.
In normal mature tissues, DUSP9 is mainly expressed in kidney, adipose tissue and placenta, while it is only minimally present in brain, ovary, testis and urinary bladder (National Center for Biotechnology Information: available online: https://www.ncbi.nlm.nih.gov/gene/1852, accessed on 15 July 2021) [25][41][42]. In order to maintain cell homeostasis, the level and activity of DUSP9 has to be tightly regulated at transcriptional, post-transcriptional and post-translational levels (Figure 2) [3]. At the transcriptional level, the expression of DUSP9 can be regulated by various transcription factors such as EFS family members and hypoxia-inducible factor 1 alpha (HIF1α). For instance, genetic depletion by gene knock-down or digoxin-induced pharmacological inhibition of HIF1 blocks the expression of DUSP9 and induces the loss of its inhibitory effect on the ERK signaling pathway in MDA-MB-231 breast cancer cells [11]. Thus, HIF1 positively regulates DUSP9 expression. DUSP9 is also transcriptionally regulated by BMP signaling in mouse embryonic stem cells (mESCs). The bone morphogenetic protein 4 (Bmp4) induces the recruitment of Smad1/5 and Smad4 on the promoter region of DUSP9 and induces DUSP9 expression at the mRNA level, and thus at the protein level. The positive regulation of DUSP9 by Bmp4 is accompanied by inhibition of ERK pathway activity and downregulation of its targets Egr1 and Fos (Figure 2). This DUSP9-mediated dephosphorylation was not observed for p38 and JNK, showing its specificity for ERK1/2 signaling which is crucial for the renewal and differentiation of mESCs [24]. In the same cells, DUSP9 can also undergo post-translational regulation by a long non-coding RNA (lncRNA) called LincU [43]. Following induced expression of LincU by the transcription factor Nanog, this lncRNA directly binds DUSP9 and maintains the phosphatase in an active and stable conformation. As a result, DUSP9, bound to LincU, constantly dephosphorylates ERK1/2 and thus, totally blocks RAS/RAF/MEK/ERK signaling. Interestingly, the phosphorylation level of ERK1/2 was inversely correlated with LincU expression and the amount of DUSP9 protein, while the level of DUSP9 mRNA remained unchanged [43]. Thus, LincU interacts with DUSP9 protein and stabilizes it in an active state, thereby triggering a constitutive dephosphorylation state of DUSP9 kinase substrates (Figure 2) [43]. DUSP9 can also be transcriptionally regulated by the retinoic acid receptor (RAR). Microarray analysis of differential gene expression in Caco-2 cells treated with RAR agonists, Ch55 and Am580 demonstrated dose-dependent induction of DUSP9 expression by RAR signaling. DUSP9 was one of the most induced genes after RAR activation. Induction of DUSP9 mRNA and protein by RAR signaling was confirmed by RT-qPCR and immunolabelling [44]. Similar results were obtained with HT29 and HeLa cells. On the other hand, DUSP9 induction was inhibited in Caco-2 cells expressing the dominant negative form of RARα or treated by the specific RAR antagonist LE540. Chromatin immunoprecipitation analysis showed that RAR induces DUSP9 expression by binding directly to the DUSP9 promoter through an inverted direct repeat separated by 1 (DR1 element). By inducing DUSP9, RAR signaling inactivates ERK during the differentiation of colorectal cancer (CRC) cells [44]. In a more recent paper, an upregulation of DUSP9 was also reported in rat ovaries following Estrogen Receptor-beta signaling induction, supporting the hypothesis that DUSP9 is one of the key genes involved in gonadotrophin-mediated ovarian follicle development [45].
In the cytoplasm, DUSP9 can be degraded by the proteasome following its ubiquitination [3][43]. Pretreatment with the potent proteasome inhibitor MG132 stabilizes DUSP9 protein and increases its level in LincU-deficient mESCs [43]. These data indicate that the ubiquitination-proteasome pathway is involved in the degradation of DUSP9 induced by LincU deficiency. Immunoprecipitation performed after pretreatment with MG132 and immunolabelling with an anti-ubiquitin antibody showed polyubiquitinated DUSP9 bands, suggesting that the knockdown of LincU causes ubiquitination of DUSP9 [43]. This indicates that LincU binds to DUSP9, increases its stability and protects it from ubiquitin-mediated degradation [3][43].

References

  1. Keshet, Y.; Seger, R. The MAP Kinase Signaling Cascades: A System of Hundreds of Components Regulates a Diverse Array of Physiological Functions. In MAP Kinase Signaling Protocols; Seger, R., Ed.; Methods in Molecular Biology; Humana Press: Totowa, NJ, USA, 2010; Volume 661, pp. 3–38. ISBN 978-1-60761-794-5.
  2. Jiang, L.; Wang, Y.; Liu, G.; Liu, H.; Zhu, F.; Ji, H.; Li, B. C-Phycocyanin Exerts Anti-Cancer Effects via the MAPK Signaling Pathway in MDA-MB-231 Cells. Cancer Cell Int. 2018, 18, 12.
  3. Chen, H.-F.; Chuang, H.-C.; Tan, T.-H. Regulation of Dual-Specificity Phosphatase (DUSP) Ubiquitination and Protein Stability. Int. J. Mol. Sci. 2019, 20, 2668.
  4. Cuenda, A.; Rousseau, S. P38 MAP-Kinases Pathway Regulation, Function and Role in Human Diseases. Biochim. Biophys. Acta (BBA)—Mol. Cell Res. 2007, 1773, 1358–1375.
  5. Gaestel, M. MAPK-Activated Protein Kinases (MKs): Novel Insights and Challenges. Front. Cell Dev. Biol. 2016, 3, 88.
  6. Morrison, D.K. MAP Kinase Pathways. Cold Spring Harb. Perspect. Biol. 2012, 4, a011254.
  7. Burotto, M.; Chiou, V.L.; Lee, J.-M.; Kohn, E.C. The MAPK Pathway across Different Malignancies: A New Perspective: Tissue-Specific MAPK Signaling. Cancer 2014, 120, 3446–3456.
  8. Nayak, J.; Gastonguay, A.J.; Talipov, M.R.; Vakeel, P.; Span, E.A.; Kalous, K.S.; Kutty, R.G.; Jensen, D.R.; Pokkuluri, P.R.; Sem, D.S.; et al. Protein Expression, Characterization and Activity Comparisons of Wild Type and Mutant DUSP5 Proteins. BMC Biochem. 2014, 15, 27.
  9. Shen, Z.; Zhang, C.; Qu, L.; Lu, C.; Xiao, M.; Ni, R.; Liu, J. MKP-4 Suppresses Hepatocarcinogenesis by Targeting ERK1/2 Pathway. Cancer Cell Int. 2019, 19, 61.
  10. Huang, C.-Y.; Tan, T.-H. DUSPs, to MAP Kinases and Beyond. Cell Biosci. 2012, 2, 24.
  11. Lu, H.; Tran, L.; Park, Y.; Chen, I.; Lan, J.; Xie, Y.; Semenza, G.L. Reciprocal Regulation of DUSP9 and DUSP16 Expression by HIF1 Controls ERK and P38 MAP Kinase Activity and Mediates Chemotherapy-Induced Breast Cancer Stem Cell Enrichment. Cancer Res. 2018, 78, 4191–4202.
  12. Muda, M.; Boschert, U.; Smith, A.; Antonsson, B.; Gillieron, C.; Chabert, C.; Camps, M.; Martinou, I.; Ashworth, A.; Arkinstall, S. Molecular Cloning and Functional Characterization of a Novel Mitogen-Activated Protein Kinase Phosphatase, MKP-4. J. Biol. Chem. 1997, 272, 5141–5151.
  13. Camps, M.; Nichols, A.; Gillieron, C.; Antonsson, B.; Muda, M.; Chabert, C.; Boschert, U.; Arkinstall, S. Catalytic Activation of the Phosphatase MKP-3 by ERK2 Mitogen-Activated Protein Kinase. Science 1998, 280, 1262–1265.
  14. Buffet, C. Anomalies Moléculaires de la Voie MAPK et Cancer Papillaire de la Thyroïde: Étude de Deux Phosphatases Spécifiques de ERK, DUSP5 et DUSP6. Ph.D. Thesis, Université René Descartes, Paris, France, 2015.
  15. Shen, J.; Zhang, Y.; Yu, H.; Shen, B.; Liang, Y.; Jin, R.; Liu, X.; Shi, L.; Cai, X. Role of DUSP1/MKP1 in Tumorigenesis, Tumor Progression and Therapy. Cancer Med. 2016, 5, 2061–2068.
  16. Wei, W.; Jiao, Y.; Postlethwaite, A.; Stuart, J.M.; Wang, Y.; Sun, D.; Gu, W. Dual-Specificity Phosphatases 2: Surprising Positive Effect at the Molecular Level and a Potential Biomarker of Diseases. Genes Immun. 2013, 14, 1–6.
  17. Hsiao, W.-Y.; Lin, Y.-C.; Liao, F.-H.; Chan, Y.-C.; Huang, C.-Y. Dual-Specificity Phosphatase 4 Regulates STAT5 Protein Stability and Helper T Cell Polarization*. PLoS ONE 2015, 10, e0145880.
  18. Menyhart, O.; Budczies, J.; Munkácsy, G.; Esteva, F.J.; Szabó, A.; Miquel, T.P.; Győrffy, B. DUSP4 Is Associated with Increased Resistance against Anti-HER2 Therapy in Breast Cancer. Oncotarget 2017, 8, 77207–77218.
  19. Seo, H.; Cho, Y.-C.; Ju, A.; Lee, S.; Park, B.C.; Park, S.G.; Kim, J.-H.; Kim, K.; Cho, S. Dual-Specificity Phosphatase 5 Acts as an Anti-Inflammatory Regulator by Inhibiting the ERK and NF-ΚB Signaling Pathways. Sci. Rep. 2017, 7, 17348.
  20. Muhammad, K.A.; Nur, A.A.; Nurul, H.S.; Narazah, M.Y.; Siti, R.A.R. Dual-Specificity Phosphatase 6 (DUSP6): A Review of Its Molecular Characteristics and Clinical Relevance in Cancer. Cancer Biol. Med. 2018, 15, 14.
  21. Luan, T.; Zhang, X.; Wang, S.; Song, Y.; Zhou, S.; Lin, J.; An, W.; Yuan, W.; Yang, Y.; Cai, H.; et al. Long Non-Coding RNA MIAT Promotes Breast Cancer Progression and Functions as CeRNA to Regulate DUSP7 Expression by Sponging MiR-155-5p. Oncotarget 2017, 8, 76153–76164.
  22. Ding, T.; Zhou, Y.; Long, R.; Chen, C.; Zhao, J.; Cui, P.; Guo, M.; Liang, G.; Xu, L. DUSP8 Phosphatase: Structure, Functions, Expression Regulation and the Role in Human Diseases. Cell Biosci. 2019, 9, 70.
  23. Jiang, L.; Ren, L.; Guo, X.; Zhao, J.; Zhang, H.; Chen, S.; Le, S.; Liu, H.; Ye, P.; Chen, M.; et al. Dual-Specificity Phosphatase 9 Protects against Cardiac Hypertrophy by Targeting ASK1. Int. J. Biol. Sci. 2021, 17, 2193–2204.
  24. Li, Z.; Fei, T.; Zhang, J.; Zhu, G.; Wang, L.; Lu, D.; Chi, X.; Teng, Y.; Hou, N.; Yang, X.; et al. BMP4 Signaling Acts via Dual-Specificity Phosphatase 9 to Control ERK Activity in Mouse Embryonic Stem Cells. Cell Stem Cell 2012, 10, 171–182.
  25. Wei, Q.; Pu, X.; Zhang, L.; Xu, Y.; Duan, M.; Wang, Y. Expression of Dual-Specificity Phosphatase 9 in Placenta and Its Relationship with Gestational Diabetes Mellitus. J. Diabetes Res. 2019, 2019, 1–7.
  26. Wu, S.; Wang, Y.; Sun, L.; Zhang, Z.; Jiang, Z.; Qin, Z.; Han, H.; Liu, Z.; Li, X.; Tang, A.; et al. Decreased Expression of Dual-Specificity Phosphatase 9 Is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma. BMC Cancer 2011, 11, 413.
  27. Ye, P.; Xiang, M.; Liao, H.; Liu, J.; Luo, H.; Wang, Y.; Huang, L.; Chen, M.; Xia, J. Dual-Specificity Phosphatase 9 Protects Against Nonalcoholic Fatty Liver Disease in Mice through ASK1 Suppression: Steatohepatitis/Metabolic Liver Disease. Hepatology 2019, 69, 76–93.
  28. Jimenez, T.; Barrios, A.; Tucker, A.; Collazo, J.; Arias, N.; Fazel, S.; Halim, M.; Huynh, T.; Singh, R.; Pervin, S. DUSP9-Mediated Reduction of PERK1/2 Supports Cancer Stem Cell-like Traits and Promotes Triple Negative Breast Cancer. Am. J. Cancer Res. 2020, 10, 3487–3506.
  29. Wu, Y.-K.; Hu, L.-F.; Lou, D.-S.; Wang, B.-C.; Tan, J. Targeting DUSP16/TAK1 Signaling Alleviates Hepatic Dyslipidemia and Inflammation in High Fat Diet (HFD)-Challenged Mice through Suppressing JNK MAPK. Biochem. Biophys. Res. Commun. 2020, 524, 142–149.
  30. Yang, C.-Y.; Li, J.-P.; Chiu, L.-L.; Lan, J.-L.; Chen, D.-Y.; Chuang, H.-C.; Huang, C.-Y.; Tan, T.-H. Dual-Specificity Phosphatase 14 (DUSP14/MKP6) Negatively Regulates TCR Signaling by Inhibiting TAB1 Activation. J. Immunol. 2014, 192, 1547–1557.
  31. Jung, S.; Nah, J.; Han, J.; Choi, S.-G.; Kim, H.; Park, J.; Pyo, H.-K.; Jung, Y.-K. Dual-Specificity Phosphatase 26 (DUSP26) Stimulates Aβ42 Generation by Promoting Amyloid Precursor Protein Axonal Transport during Hypoxia. J. Neurochem. 2016, 137, 770–781.
  32. Low, H.B.; Zhang, Y. Regulatory Roles of MAPK Phosphatases in Cancer. Immune Netw. 2016, 16, 85–98.
  33. Seternes, O.-M.; Kidger, A.M.; Keyse, S.M. Dual-Specificity MAP Kinase Phosphatases in Health and Disease. Biochim. Biophys. Acta (BBA)—Mol. Cell Res. 2019, 1866, 124–143.
  34. Keyse, S.M. Dual-Specificity MAP Kinase Phosphatases (MKPs) and Cancer. Cancer Metastasis Rev. 2008, 27, 253–261.
  35. Lang, R.; Hammer, M.; Mages, J. DUSP Meet Immunology: Dual Specificity MAPK Phosphatases in Control of the Inflammatory Response. J. Immunol. 2006, 177, 7497–7504.
  36. Lang, R.; Raffi, F.A.M. Dual-Specificity Phosphatases in Immunity and Infection: An Update. Int. J. Mol. Sci. 2019, 20, 2710.
  37. Theodosiou, A.; Ashworth, A. MAP Kinase Phosphatases. Genome Biol. 2002, 3, REVIEWS3009.
  38. Jeong, D.G.; Yoon, T.S.; Jung, S.K.; Park, B.C.; Park, H.; Ryu, S.E.; Kim, S.J. Exploring Binding Sites Other than the Catalytic Core in the Crystal Structure of the Catalytic Domain of MKP-4. Acta Crystallogr. D Biol. Crystallogr. 2011, 67, 25–31.
  39. Hong, S.B.; Lubben, T.H.; Dolliver, C.M.; Petrolonis, A.J.; Roy, R.A.; Li, Z.; Parsons, T.F.; Li, P.; Xu, H.; Reilly, R.M.; et al. Expression, Purification, and Enzymatic Characterization of the Dual Specificity Mitogen-Activated Protein Kinase Phosphatase, MKP-4. Bioorg. Chem. 2005, 33, 34–44.
  40. Sehnal, D.; Bittrich, S.; Deshpande, M.; Svobodová, R.; Berka, K.; Bazgier, V.; Velankar, S.; Burley, S.K.; Koča, J.; Rose, A.S. Mol* Viewer: Modern Web App for 3D Visualization and Analysis of Large Biomolecular Structures. Nucleic Acids Res. 2021, 49, W431–W437.
  41. Uhlén, M.; Björling, E.; Agaton, C.; Szigyarto, C.A.-K.; Amini, B.; Andersen, E.; Andersson, A.-C.; Angelidou, P.; Asplund, A.; Asplund, C.; et al. A Human Protein Atlas for Normal and Cancer Tissues Based on Antibody Proteomics. Mol. Cell. Proteom. 2005, 4, 1920–1932.
  42. Xu, H.; Dembski, M.; Yang, Q.; Yang, D.; Moriarty, A.; Tayber, O.; Chen, H.; Kapeller, R.; Tartaglia, L.A. Dual Specificity Mitogen-Activated Protein (MAP) Kinase Phosphatase-4 Plays a Potential Role in Insulin Resistance. J. Biol. Chem. 2003, 278, 30187–30192.
  43. Jiapaer, Z.; Li, G.; Ye, D.; Bai, M.; Li, J.; Guo, X.; Du, Y.; Su, D.; Jia, W.; Chen, W.; et al. LincU Preserves Naive Pluripotency by Restricting ERK Activity in Embryonic Stem Cells. Stem Cell Rep. 2018, 11, 395–409.
  44. Imajo, M.; Kondoh, K.; Yamamoto, T.; Nakayama, K.; Nakajima-Koyama, M.; Nishida, E. Antagonistic Interactions between Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase and Retinoic Acid Receptor Signaling in Colorectal Cancer Cells. Mol. Cell. Biol. 2017, 37.
  45. Chakravarthi, V.P.; Ratri, A.; Masumi, S.; Borosha, S.; Ghosh, S.; Christenson, L.K.; Roby, K.F.; Wolfe, M.W.; Rumi, M.A.K. Granulosa Cell Genes That Regulate Ovarian Follicle Development beyond the Antral Stage: The Role of Estrogen Receptor β. Mol. Cell. Endocrinol. 2021, 528, 111212.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Cell Biology
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Christophe Grosset
View Times: 416
Revisions: 2 times (View History)
Update Date: 08 Nov 2021
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback