Gene Symbol: Dusp6
Description: dual specificity phosphatase 6
Alias: 1300019I03Rik, MKP-3, MKP3, PYST1, dual specificity protein phosphatase 6, MAP kinase phosphatase 3, mitogen-activated protein kinase phosphatase 3
Species: mouse
Products:     Dusp6

Top Publications

  1. Dickinson R, Eblaghie M, Keyse S, Morriss Kay G. Expression of the ERK-specific MAP kinase phosphatase PYST1/MKP3 in mouse embryos during morphogenesis and early organogenesis. Mech Dev. 2002;113:193-6 pubmed
    ..We have studied embryonic expression of the dual-specificity MAP kinase phosphatase PYST1/MKP3, which is a specific and potent regulator of the ERK class of MAP kinases...
  2. Maillet M, Purcell N, Sargent M, York A, Bueno O, Molkentin J. DUSP6 (MKP3) null mice show enhanced ERK1/2 phosphorylation at baseline and increased myocyte proliferation in the heart affecting disease susceptibility. J Biol Chem. 2008;283:31246-55 pubmed publisher
    ..dephosphorylation plays in vivo through targeted disruption of the gene encoding dual-specificity phosphatase 6 (Dusp6) in the mouse...
  3. Kawakami Y, Rodriguez Leon J, Koth C, Buscher D, Itoh T, Raya A, et al. MKP3 mediates the cellular response to FGF8 signalling in the vertebrate limb. Nat Cell Biol. 2003;5:513-9 pubmed
    ..Here we show that during chick, mouse and zebrafish limb/fin development, a known MAPK/ERK regulator, Mkp3, is induced in the mesenchyme by fibroblast growth factor 8 (FGF8) signalling, through the PI3K/Akt pathway...
  4. Wu Z, Jiao P, Huang X, Feng B, Feng Y, Yang S, et al. MAPK phosphatase-3 promotes hepatic gluconeogenesis through dephosphorylation of forkhead box O1 in mice. J Clin Invest. 2010;120:3901-11 pubmed publisher
    ..These data indicate that MKP-3 is an important regulator of hepatic gluconeogenesis in vivo and suggest that inhibition of MKP-3 activity may provide new therapies for T2DM. ..
  5. Morrison D, Kim M, Berkofsky Fessler W, Licht J. WT1 induction of mitogen-activated protein kinase phosphatase 3 represents a novel mechanism of growth suppression. Mol Cancer Res. 2008;6:1225-31 pubmed publisher
    ..we show that WT1 transactivates another important negative regulator of the Ras/MAPK pathway, MAPK phosphatase 3 (MKP3)...
  6. Li C, Scott D, Hatch E, Tian X, Mansour S. Dusp6 (Mkp3) is a negative feedback regulator of FGF-stimulated ERK signaling during mouse development. Development. 2007;134:167-76 pubmed
    ..We show here that in mouse embryos, Fibroblast growth factor receptors (FGFRs) are required for transcription of Dusp6, which encodes MKP3, an extracellular signal-regulated kinase (ERK)-specific MKP...
  7. Zhang Y, Wu J, Wang Z. Mitogen-activated protein kinase (MAPK) phosphatase 3-mediated cross-talk between MAPKs ERK2 and p38alpha. J Biol Chem. 2011;286:16150-62 pubmed publisher
    MAPK phosphatase 3 (MKP3) is highly specific for ERK1/2 inactivation via dephosphorylation of both phosphotyrosine and phosphothreonine critical for enzymatic activation...
  8. Karlsson M, Mathers J, Dickinson R, Mandl M, Keyse S. Both nuclear-cytoplasmic shuttling of the dual specificity phosphatase MKP-3 and its ability to anchor MAP kinase in the cytoplasm are mediated by a conserved nuclear export signal. J Biol Chem. 2004;279:41882-91 pubmed
    ..Our results reinforce the idea that regulatory proteins such as MKP-3 may play a key role in the spatio-temporal regulation of MAP kinase activity. ..
  9. Echevarria D, Martinez S, Marques S, Lucas Teixeira V, Belo J. Mkp3 is a negative feedback modulator of Fgf8 signaling in the mammalian isthmic organizer. Dev Biol. 2005;277:114-28 pubmed
    ..In chick limb bud development, a dual mitogen-activated protein kinase phosphatase-3 (Mkp3) plays a role as a negative feedback modulator of Fgf8 signaling...

More Information


  1. Ashe A, Butterfield N, Town L, Courtney A, Cooper A, Ferguson C, et al. Mutations in mouse Ift144 model the craniofacial, limb and rib defects in skeletal ciliopathies. Hum Mol Genet. 2012;21:1808-23 pubmed publisher
    ..This allelic series of mouse mutants provides a unique opportunity to uncover the underlying mechanistic basis of this intriguing subset of ciliopathies. ..
  2. Smith T, Karlsson M, Lunn J, Eblaghie M, Keenan I, Farrell E, et al. Negative feedback predominates over cross-regulation to control ERK MAPK activity in response to FGF signalling in embryos. FEBS Lett. 2006;580:4242-5 pubmed
    Expression of the gene encoding the MKP-3/Pyst1 protein phosphatase, which inactivates ERK MAPK, is induced by FGF...
  3. Pfuhlmann K, Pfluger P, Schriever S, Müller T, Tschop M, Stemmer K. Dual specificity phosphatase 6 deficiency is associated with impaired systemic glucose tolerance and reversible weight retardation in mice. PLoS ONE. 2017;12:e0183488 pubmed publisher
    Here, we aimed to investigate the potential role of DUSP6, a dual specificity phosphatase, that specifically inactivates extracellular signal-regulated kinase (ERK), for the regulation of body weight and glucose homeostasis...
  4. Zeller E, Mock K, Horn M, Colnot S, Schwarz M, Braeuning A. Dual-specificity phosphatases are targets of the Wnt/?-catenin pathway and candidate mediators of ?-catenin/Ras signaling interactions. Biol Chem. 2012;393:1183-91 pubmed publisher
    ..In addition, we identified a ?-catenin-binding site within the Dusp6 promoter, which is responsible for the activation of the promoter by ?-catenin signaling, and demonstrated reduced ..
  5. Delgado I, Dominguez Frutos E, Schimmang T, Ros M. The incomplete inactivation of Fgf8 in the limb ectoderm affects the morphogenesis of the anterior autopod through BMP-mediated cell death. Dev Dyn. 2008;237:649-58 pubmed publisher
    ..These limbs also exhibit an abnormal area of cell death at the anterior forelimb autopod, overlapping with an ectopic domain of Bmp7 expression, which can explain the abnormal morphogenesis of the anterior autopod. ..
  6. Talamillo A, Delgado I, Nakamura T, de Vega S, Yoshitomi Y, Unda F, et al. Role of Epiprofin, a zinc-finger transcription factor, in limb development. Dev Biol. 2010;337:363-74 pubmed publisher
  7. Bagnyukova T, Restifo D, Beeharry N, Gabitova L, Li T, Serebriiskii I, et al. DUSP6 regulates drug sensitivity by modulating DNA damage response. Br J Cancer. 2013;109:1063-71 pubmed publisher
    Dual specificity phosphatase 6 (DUSP6) is a member of a family of mitogen-activated protein kinase phosphatases that dephosphorylates and inhibits activated ERK1/2...
  8. James M, Järvinen E, Wang X, Thesleff I. Different roles of Runx2 during early neural crest-derived bone and tooth development. J Bone Miner Res. 2006;21:1034-44 pubmed
    ..Genes downregulated in tooth development were Dkk1, Dusp6, Enpp1, and Igfbp3. These genes were all induced by fibroblast growth factors (FGFs) in dental tissue...
  9. Koo J, Wang S, Kang N, Hur S, Bahk Y. Induction of MAP kinase phosphatase 3 through Erk/MAP kinase activation in three oncogenic Ras (H-, K- and N-Ras)-expressing NIH/3T3 mouse embryonic fibroblast cell lines. BMB Rep. 2016;49:370-5 pubmed
    ..In the present study, using three inducible Ras-expressing NIH/3T3 cell lines, we demonstrated that MKP3 upregulation requires the activation of the Erk1/2 pathway, which correlates with the shutdown of this pathway...
  10. Marshall G, Liu P, Gherardi S, Scarlett C, Bedalov A, Xu N, et al. SIRT1 promotes N-Myc oncogenesis through a positive feedback loop involving the effects of MKP3 and ERK on N-Myc protein stability. PLoS Genet. 2011;7:e1002135 pubmed publisher
    ..form a novel transcriptional repressor complex at gene promoter of mitogen-activated protein kinase phosphatase 3 (MKP3), leading to transcriptional repression of MKP3, ERK protein phosphorylation, N-Myc protein phosphorylation at ..
  11. Hippenmeyer S, Huber R, Ladle D, Murphy K, Arber S. ETS transcription factor Erm controls subsynaptic gene expression in skeletal muscles. Neuron. 2007;55:726-40 pubmed
    ..Together, our findings define Erm as an upstream regulator of a transcriptional program selective to subsynaptic nuclei at the NMJ and underscore the importance of transcriptional control of local synaptic protein accumulation. ..
  12. Miraoui H, Dwyer A, Sykiotis G, Plummer L, CHUNG W, Feng B, et al. Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am J Hum Genet. 2013;92:725-43 pubmed publisher
    ..and SPRY2, all other genes were found to be mutated in CHH individuals: FGF17 (n = 3 individuals), IL17RD (n = 8), DUSP6 (n = 5), SPRY4 (n = 14), and FLRT3 (n = 3)...
  13. Miller K, Ah Cann C, Welfare M, Tan T, Pope K, Caruana G, et al. Cauli: a mouse strain with an Ift140 mutation that results in a skeletal ciliopathy modelling Jeune syndrome. PLoS Genet. 2013;9:e1003746 pubmed publisher
    ..We also report the identification of a homozygous recessive mutation in IFT140 in a Jeune syndrome patient. This ENU-induced Jeune syndrome model will be useful in delineating the origins of dysmorphology in human ciliopathies. ..
  14. Finelli M, Murphy K, Chen L, Zou H. Differential phosphorylation of Smad1 integrates BMP and neurotrophin pathways through Erk/Dusp in axon development. Cell Rep. 2013;3:1592-606 pubmed publisher
    ..linker phosphorylation of Smad1 (pSmad1L), which in turn upregulates an Erk-specific dual-specificity phosphatase, Dusp6, leading to reduced pErk1/2 and constituting a negative-feedback loop for the prevention of axon overgrowth...
  15. Saha M, Skopelja S, Martinez E, Alvarez D, Liponis B, Romero Sandoval E. Spinal mitogen-activated protein kinase phosphatase-3 (MKP-3) is necessary for the normal resolution of mechanical allodynia in a mouse model of acute postoperative pain. J Neurosci. 2013;33:17182-7 pubmed publisher
  16. Green R, Feng W, Phang T, Fish J, Li H, Spritz R, et al. Tfap2a-dependent changes in mouse facial morphology result in clefting that can be ameliorated by a reduction in Fgf8 gene dosage. Dis Model Mech. 2015;8:31-43 pubmed publisher
    ..Overall, our findings suggest that CL/P can result from small gene-expression changes that alter the shape of the facial prominences and uncouple their coordinated morphogenesis, which is necessary for normal fusion. ..
  17. Norrie J, Lewandowski J, Bouldin C, Amarnath S, Li Q, Vokes M, et al. Dynamics of BMP signaling in limb bud mesenchyme and polydactyly. Dev Biol. 2014;393:270-281 pubmed publisher
    ..Our results provide new insights into the timing and clarify the mechanisms underlying BMP signaling during digit morphogenesis. ..
  18. Lin M, Chang K, Lin S, Miner J. Epidermal hyperproliferation in mice lacking fatty acid transport protein 4 (FATP4) involves ectopic EGF receptor and STAT3 signaling. Dev Biol. 2010;344:707-19 pubmed publisher
    ..These findings have important implications for understanding the pathogenesis of ichthyosis prematurity syndrome, a disease recently shown to be caused by FATP4 mutations. ..
  19. Klock A, Herrmann B. Cloning and expression of the mouse dual-specificity mitogen-activated protein (MAP) kinase phosphatase Mkp3 during mouse embryogenesis. Mech Dev. 2002;116:243-7 pubmed
    ..In this report, we describe the cloning and expression analysis of the mouse Mkp3 gene...
  20. Eblaghie M, Song S, Kim J, Akita K, Tickle C, Jung H. Interactions between FGF and Wnt signals and Tbx3 gene expression in mammary gland initiation in mouse embryos. J Anat. 2004;205:1-13 pubmed
    ..the human condition ulnar-mammary syndrome, expression of the gene encoding the dual-specificity MAPK phosphatase Pyst1/MKP3, which is an early response to FGFR1 signalling (as judged by sensitivity to the SU5402 inhibitor), and ..
  21. Feng B, Jiao P, Yang Z, Xu H. MEK/ERK pathway mediates insulin-promoted degradation of MKP-3 protein in liver cells. Mol Cell Endocrinol. 2012;361:116-23 pubmed publisher
    b>MAP kinase phosphatase 3 (MKP-3) was recently identified as an important regulator of glucose homeostasis in the liver and its expression can be repressed by insulin at post transcriptional level...
  22. Akiyama R, Kawakami H, Taketo M, Evans S, Wada N, Petryk A, et al. Distinct populations within Isl1 lineages contribute to appendicular and facial skeletogenesis through the ?-catenin pathway. Dev Biol. 2014;387:37-48 pubmed publisher
  23. Jeong H, Park K, Kim D. PP2A and DUSP6 are involved in sphingosylphosphorylcholine-induced hypopigmentation. Mol Cell Biochem. 2012;367:43-9 pubmed publisher
    ..that ?-melanocyte-stimulating hormone (?-MSH) increased the expression of dual-specificity phosphatase 6 (DUSP6), an ERK phosphatase, in a time-dependent manner. In contrast, SPC decreased the level of DUSP6 in Mel-Ab cells...
  24. Feng B, Jiao P, Helou Y, Li Y, He Q, Walters M, et al. Mitogen-activated protein kinase phosphatase 3 (MKP-3)-deficient mice are resistant to diet-induced obesity. Diabetes. 2014;63:2924-34 pubmed publisher
    ..33-fold. Activities of HDAC1 and 2 are increased in the livers of MKP-3(-/-) mice fed an HFD. Reduction of HDAC1/2 activities is sufficient to restore TG content of MKP-3(-/-) primary hepatocytes to a level similar to that in WT cells. ..
  25. Shimokawa K, Kimura Yoshida C, Nagai N, Mukai K, Matsubara K, Watanabe H, et al. Cell surface heparan sulfate chains regulate local reception of FGF signaling in the mouse embryo. Dev Cell. 2011;21:257-72 pubmed publisher
    ..Together, the results show that spatiotemporal expression of cell surface-tethered HS chains regulate the local reception of FGF-signaling activity during mammalian embryogenesis. ..
  26. Zhang Z, Sui P, Dong A, Hassell J, Cserjesi P, Chen Y, et al. Preaxial polydactyly: interactions among ETV, TWIST1 and HAND2 control anterior-posterior patterning of the limb. Development. 2010;137:3417-26 pubmed publisher
    ..Together, our data suggest that through biochemical interactions, the Shh expression regulators ETV, TWIST1 and HAND2 attain a precise balance to establish anterior-posterior patterning of the limb...
  27. Gardiner J, Jackson A, Gordon J, Lickert H, Manley N, Basson M. Localised inhibition of FGF signalling in the third pharyngeal pouch is required for normal thymus and parathyroid organogenesis. Development. 2012;139:3456-66 pubmed publisher
  28. Ruan J, Statt S, Huang C, Tsai Y, Kuo C, Chan H, et al. Dual-specificity phosphatase 6 deficiency regulates gut microbiome and transcriptome response against diet-induced obesity in mice. Nat Microbiol. 2016;2:16220 pubmed publisher
    ..b>Dusp6-deficient mice have been shown to be resistant to diet-induced obesity, but the mechanism behind this remains ..
  29. Martinez Ferre A, Martinez S. The development of the thalamic motor learning area is regulated by Fgf8 expression. J Neurosci. 2009;29:13389-400 pubmed publisher
    ..This region specializes to permit the development of adaptive control of the motor function in the vertebrate brain. ..
  30. Huang X, Liao W, Huang Y, Jiang M, Chen J, Wang M, et al. Neuroprotective effect of dual specificity phosphatase 6 against glutamate-induced cytotoxicity in mouse hippocampal neurons. Biomed Pharmacother. 2017;91:385-392 pubmed publisher
    Dual specificity phosphatase 6 (DUSP6), a member of the dual specificity protein phosphatase subfamily, can inactivate ERK1/2. However, its possible role in glutamate-induced oxidative cytotoxicity effects is not clear...
  31. Hayashi S, Akiyama R, Wong J, Tahara N, Kawakami H, Kawakami Y. Gata6-Dependent GLI3 Repressor Function is Essential in Anterior Limb Progenitor Cells for Proper Limb Development. PLoS Genet. 2016;12:e1006138 pubmed publisher
    ..Both the genetic and biochemical data elucidates a novel mechanism by Gata6 to regulate GLI3R activities in the anterior limb progenitor cells to prevent polydactyly and attain proper development of the mammalian autopod. ..
  32. Jiao P, Feng B, Xu H. Mapping MKP-3/FOXO1 interaction and evaluating the effect on gluconeogenesis. PLoS ONE. 2012;7:e41168 pubmed publisher
    b>MAP kinase phosphatase 3 (MKP-3) is known to attenuate the ERK signaling pathway. It has been recently demonstrated that MKP-3 is also a player in promoting hepatic glucose output in obese state by interacting and activating FOXO1...
  33. Li W, Song L, Ritchie A, Melton D. Increased levels of DUSP6 phosphatase stimulate tumourigenesis in a molecularly distinct melanoma subtype. Pigment Cell Melanoma Res. 2012;25:188-99 pubmed publisher
    The mitogen-activated protein kinase (MAPK) pathway is important in melanoma. In this pathway, DUSP6 phosphatase negatively controls the activation of extracellular signal-regulated (ERK) kinase...
  34. Yashiro K, Zhao X, Uehara M, Yamashita K, Nishijima M, Nishino J, et al. Regulation of retinoic acid distribution is required for proximodistal patterning and outgrowth of the developing mouse limb. Dev Cell. 2004;6:411-22 pubmed
    ..These observations suggest that RA acts as a morphogen to determine proximodistal identity, and that CYP26B1 prevents apoptosis and promotes chondrocyte maturation, in the developing limb. ..
  35. Bénazet J, Zeller R. Dual requirement of ectodermal Smad4 during AER formation and termination of feedback signaling in mouse limb buds. Genesis. 2013;51:660-6 pubmed publisher
    ..In summary, our genetic analysis reveals the temporally and functionally distinct dual requirement of ectodermal Smad4 during initiation and termination of AER signaling. ..
  36. Feng B, He Q, Xu H. FOXO1-dependent up-regulation of MAP kinase phosphatase 3 (MKP-3) mediates glucocorticoid-induced hepatic lipid accumulation in mice. Mol Cell Endocrinol. 2014;393:46-55 pubmed publisher
  37. Mariani F, Ahn C, Martin G. Genetic evidence that FGFs have an instructive role in limb proximal-distal patterning. Nature. 2008;453:401-5 pubmed publisher
    ..We discuss how a two-signal model for P-D patterning can be integrated with the concept of early specification to explain the genetic data presented here. ..
  38. Liu B. Association of the dusp6 (mkp3) gene with mouse brain weight and forebrain structure. J Child Neurol. 2008;23:624-7 pubmed publisher
    ..The Dusp6 (Mkp3) gene is also highly expressed in the mouse embryonic forebrain...
  39. Lu P, Yu Y, Perdue Y, Werb Z. The apical ectodermal ridge is a timer for generating distal limb progenitors. Development. 2008;135:1395-405 pubmed publisher
    ..Taken together, we have uncovered a novel mechanism, whereby the AER regulates the number of autopod progenitors by determining the onset of their generation. ..
  40. Verheyden J, Lewandoski M, Deng C, Harfe B, Sun X. Conditional inactivation of Fgfr1 in mouse defines its role in limb bud establishment, outgrowth and digit patterning. Development. 2005;132:4235-45 pubmed
    ..Our study of these two Fgfr1 conditional mutants has elucidated the multiple roles of FGFR1 in limb bud establishment, growth and patterning. ..
  41. Souza Pauli L, Ropelle E, de Souza C, Cintra D, da Silva A, de Almeida Rodrigues B, et al. Exercise training decreases mitogen-activated protein kinase phosphatase-3 expression and suppresses hepatic gluconeogenesis in obese mice. J Physiol. 2014;592:1325-40 pubmed publisher
    ..Finally, the suppressive effects of exercise training on MKP-3 protein levels appear to be related, at least in part, to the reduced phosphorylation of Extracellular signal-regulated kinases (ERK) in the livers of obese mice. ..
  42. Park Y, Lee J, Lee M, Kim Y, Shin S. c-Myb negatively regulates Ras signaling through induction of dual phosphatase MKP-3 in NIH3T3 cells. Biochem Biophys Res Commun. 2014;450:1032-7 pubmed publisher
    ..Knock-down of c-Myb expression using siRNA abrogated Ras-induced MKP-3 promoter activity. These findings propose a novel mechanism through which Ras signaling activates c-Myb-dependent transcriptional activation of the MKP-3 gene. ..
  43. Deckelbaum R, Holmes G, Zhao Z, Tong C, Basilico C, Loomis C. Regulation of cranial morphogenesis and cell fate at the neural crest-mesoderm boundary by engrailed 1. Development. 2012;139:1346-58 pubmed publisher
  44. Vasudevan H, Mazot P, He F, Soriano P. Receptor tyrosine kinases modulate distinct transcriptional programs by differential usage of intracellular pathways. elife. 2015;4: pubmed publisher
    ..Our results identify distinct responses to PDGF and FGF and provide insight into the mechanisms encoding RTK specificity. ..
  45. Reid B, Yang H, Melvin V, Taketo M, Williams T. Ectodermal Wnt/?-catenin signaling shapes the mouse face. Dev Biol. 2011;349:261-9 pubmed publisher
  46. Carson W, Salter Green S, Scola M, Joshi A, Gallagher K, Kunkel S. Enhancement of macrophage inflammatory responses by CCL2 is correlated with increased miR-9 expression and downregulation of the ERK1/2 phosphatase Dusp6. Cell Immunol. 2017;314:63-72 pubmed publisher
    ..correlated with increased phosphorylation of ERK1/2 kinases, a decrease in expression of the ERK phosphatase Dusp6 and enhanced expression of miR-9...
  47. Crespo Enríquez I, Partanen J, Martinez S, Echevarria D. Fgf8-related secondary organizers exert different polarizing planar instructions along the mouse anterior neural tube. PLoS ONE. 2012;7:e39977 pubmed publisher
  48. Qu X, Pan Y, Carbe C, Powers A, Grobe K, Zhang X. Glycosaminoglycan-dependent restriction of FGF diffusion is necessary for lacrimal gland development. Development. 2012;139:2730-9 pubmed publisher
    ..Taken together, these results demonstrate that mesenchymal GAG controls lacrimal gland induction by restricting the diffusion of Fgf10...
  49. Simrick S, Szumska D, Gardiner J, Jones K, Sagar K, Morrow B, et al. Biallelic expression of Tbx1 protects the embryo from developmental defects caused by increased receptor tyrosine kinase signaling. Dev Dyn. 2012;241:1310-24 pubmed publisher
    ..We propose that genetic factors that enhance RTK signaling ought to be considered as potential genetic modifiers of this syndrome. ..
  50. Le Grand F, Grifone R, Mourikis P, Houbron C, Gigaud C, Pujol J, et al. Six1 regulates stem cell repair potential and self-renewal during skeletal muscle regeneration. J Cell Biol. 2012;198:815-32 pubmed publisher
    ..regulates the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway during regeneration via direct control of Dusp6 transcription...
  51. Xu B, Yang L, Lye R, Hinton B. p-MAPK1/3 and DUSP6 regulate epididymal cell proliferation and survival in a region-specific manner in mice. Biol Reprod. 2010;83:807-17 pubmed publisher
    ..To understand further the regulation of cell proliferation in the IS, we examined the role of DUSP6, an MAPK1/3 (ERK1/2) preferred phosphatase that is also regulated by lumicrine factors in the IS...
  52. Mittal A, Pulina M, Hou S, Astrof S. Fibronectin and integrin alpha 5 play requisite roles in cardiac morphogenesis. Dev Biol. 2013;381:73-82 pubmed publisher
    ..We show that these defects are likely due to the requirement for cell adhesion to fibronectin for proliferation of myocardial progenitors and for Fgf8 signaling in the pharyngeal region. ..
  53. Vázquez Echeverría C, Dominguez Frutos E, Charnay P, Schimmang T, Pujades C. Analysis of mouse kreisler mutants reveals new roles of hindbrain-derived signals in the establishment of the otic neurogenic domain. Dev Biol. 2008;322:167-78 pubmed publisher
    ..These results highlight the importance of hindbrain-derived signals in the regulation of otic neurogenesis. ..
  54. Geetha N, Mihaly J, Stockenhuber A, Blasi F, Uhrin P, Binder B, et al. Signal integration and coincidence detection in the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) cascade: concomitant activation of receptor tyrosine kinases and of LRP-1 leads to sustained ERK phosphorylation via down. J Biol Chem. 2011;286:25663-74 pubmed publisher
    ..of phospho-ERK was accounted for by enhanced proteasomal degradation of dual specificity phosphatases DUSP1 and DUSP6, which precluded dephosphorylation of cytosolic ERK...
  55. Clarke M, Volpe G, Sheriff L, Walton D, Ward C, Wei W, et al. Transcriptional regulation of SPROUTY2 by MYB influences myeloid cell proliferation and stem cell properties by enhancing responsiveness to IL-3. Leukemia. 2017;31:957-966 pubmed publisher
    ..MYB acts on MAPK signaling by directly regulating transcription of the gene encoding the negative modulator SPRY2. This mechanistic insight points to pathways that might be targeted therapeutically in MPN. ..
  56. Butterfield N, Metzis V, McGlinn E, Bruce S, Wainwright B, Wicking C. Patched 1 is a crucial determinant of asymmetry and digit number in the vertebrate limb. Development. 2009;136:3515-24 pubmed publisher
    ..These results establish the importance of the downstream consequences of Hh pathway repression, and identify Ptc1 as a key player in limb patterning even prior to the onset of Shh expression. ..
  57. Tárrega C, Rios P, Cejudo Marín R, Blanco Aparicio C, van den Berk L, Schepens J, et al. ERK2 shows a restrictive and locally selective mechanism of recognition by its tyrosine phosphatase inactivators not shared by its activator MEK1. J Biol Chem. 2005;280:37885-94 pubmed
  58. Chan K, Wong H, Jin G, Liu B, Cao R, Cao Y, et al. MT1-MMP inactivates ADAM9 to regulate FGFR2 signaling and calvarial osteogenesis. Dev Cell. 2012;22:1176-90 pubmed publisher
    ..These data reveal a regulatory paradigm for FGRF2 signaling and identify MT1-MMP as a critical negative modulator of ADAM9 activity to maintain FGFR2 signaling in calvarial osteogenesis. ..
  59. Kim W, Oh K, Choi H, Park A, Han B, Chi S, et al. MAP kinase phosphatase 3 inhibits brown adipocyte differentiation via regulation of Erk phosphorylation. Mol Cell Endocrinol. 2015;416:70-6 pubmed publisher
    ..Here, we identified that MAP kinase phosphatase 3 (MKP3) has a novel role as regulator of brown adipocyte differentiation...
  60. Wang C, Gargollo P, Guo C, Tang T, Mingin G, Sun Y, et al. Six1 and Eya1 are critical regulators of peri-cloacal mesenchymal progenitors during genitourinary tract development. Dev Biol. 2011;360:186-94 pubmed publisher
    ..Thus, Six1 and Eya1 are key regulators of both upper and lower urinary tract morphogenesis. Results from this study uncover essential roles of the PCM progenitors during genitourinary tract formation...
  61. Ekerot M, Stavridis M, Delavaine L, Mitchell M, Staples C, Owens D, et al. Negative-feedback regulation of FGF signalling by DUSP6/MKP-3 is driven by ERK1/2 and mediated by Ets factor binding to a conserved site within the DUSP6/MKP-3 gene promoter. Biochem J. 2008;412:287-98 pubmed publisher
    b>DUSP6 (dual-specificity phosphatase 6), also known as MKP-3 [MAPK (mitogen-activated protein kinase) phosphatase-3] specifically inactivates ERK1/2 (extracellular-signal-regulated kinase 1/2) in vitro and in vivo...
  62. Bertin S, Lozano Ruiz B, Bachiller V, García Martínez I, Herdman S, Zapater P, et al. Dual-specificity phosphatase 6 regulates CD4+ T-cell functions and restrains spontaneous colitis in IL-10-deficient mice. Mucosal Immunol. 2015;8:505-15 pubmed publisher
    ..b>DUSP6 preferentially dephosphorylates extracellular signal-regulated kinases 1 and 2 (ERK1/2) rendering them inactive...
  63. Liang D, Wang X, Mittal A, Dhiman S, Hou S, Degenhardt K, et al. Mesodermal expression of integrin α5β1 regulates neural crest development and cardiovascular morphogenesis. Dev Biol. 2014;395:232-44 pubmed publisher
  64. Zhang Z, Verheyden J, Hassell J, Sun X. FGF-regulated Etv genes are essential for repressing Shh expression in mouse limb buds. Dev Cell. 2009;16:607-13 pubmed publisher
    ..This finding elucidates a novel aspect of the mechanism coordinating limb development along the A-P and P-D axes...
  65. Kim W, Matsui T, Yamao M, Ishibashi M, Tamada K, Takumi T, et al. The period of the somite segmentation clock is sensitive to Notch activity. Mol Biol Cell. 2011;22:3541-9 pubmed publisher
    ..Therefore we propose that the period of the somite segmentation clock is sensitive to Notch activity and that Nrarp plays essential roles in the morphology of vertebrae and ribs. ..
  66. Srivastava N, Sudan R, Saha B. CD40-modulated dual-specificity phosphatases MAPK phosphatase (MKP)-1 and MKP-3 reciprocally regulate Leishmania major infection. J Immunol. 2011;186:5863-72 pubmed publisher
    ..The findings reveal a novel parasite-devised immune evasion strategy and an effective target to redirect CD40-regulated immune responses. ..
  67. Zhang J, Nomura J, Maruyama M, Nishimoto M, Muramatsu M, Okuda A. Identification of an ES cell pluripotent state-specific DUSP6 enhancer. Biochem Biophys Res Commun. 2009;378:319-23 pubmed publisher
    ..Among the numerous genes identified, we focused on dual specificity phosphatase 6 (DUSP6), which had previously been shown to be expressed in undifferentiated human ES cells...
  68. Dudley A, Tabin C. Deconstructing phosphatases in limb development. Nat Cell Biol. 2003;5:499-501 pubmed
  69. Ihermann Hella A, Lume M, Miinalainen I, Pirttiniemi A, Gui Y, Peranen J, et al. Mitogen-activated protein kinase (MAPK) pathway regulates branching by remodeling epithelial cell adhesion. PLoS Genet. 2014;10:e1004193 pubmed publisher
    ..We show that MAPK activity is required for branching morphogenesis, and propose that it promotes cell cycle progression and higher cellular motility through remodeling of cellular adhesions. ..
  70. Seifert A, Yamaguchi T, Cohn M. Functional and phylogenetic analysis shows that Fgf8 is a marker of genital induction in mammals but is not required for external genital development. Development. 2009;136:2643-51 pubmed publisher
    ..We propose that induction of external genitalia involves an epithelial-epithelial interaction at the cloacal membrane, and suggest that the cloacal ectoderm may be the source of the genital initiation signal...
  71. Razmara M, Eger G, Rorsman C, Heldin C, Lennartsson J. MKP3 negatively modulates PDGF-induced Akt and Erk5 phosphorylation as well as chemotaxis. Cell Signal. 2012;24:635-40 pubmed publisher
    MAP kinase phosphatase-3 (MKP3), also known as DUSP6 or Pyst1, is a dual specificity phosphatase considered to selectively dephosphorylate extracellular-signal-regulated kinase 1/2 (Erk1/2)...
  72. Thomason H, Dixon M, Dixon J. Facial clefting in Tp63 deficient mice results from altered Bmp4, Fgf8 and Shh signaling. Dev Biol. 2008;321:273-82 pubmed publisher
    ..Our results are consistent with a role for Tp63 in the regulation of Bmp signaling controlling the growth, modelling and fusion events underlying facial development and shed new light on the complex abnormality of facial clefting. ..
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    ..Although ERK2 activity is regulated by its phosphorylation state, MKP3 is regulated by physical interaction with ERK2, independent of its enzymatic activity (Camps, M., Nichols, A...