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DUSP6 — MAPK1

Pathways - manually collected, often from reviews:

• OpenBEL Selventa BEL large corpus: MAPK1 → DUSP6 (directlyDecreases, DUSP6 Activity, MAPK1 Activity) Zhou et al., J Biol Chem 2002*
  Evidence: Using 32P-labeled bisphosphorylated ERK2, ERK2/pTpY (ERK2 phosphorylated on both Thr-183 and Tyr-185) as a substrate, we previously determined the kinetic parameters of the MKP3-catalyzed dephosphorylation of ERK2/pTpY by following the production of radioactive inorganic phosphate (25).
• OpenBEL Selventa BEL large corpus: MAPK1 → DUSP6 (directlyDecreases, DUSP6 Activity, MAPK1 Activity)
  Evidence: The second subfamily comprises DUSP6, DUSP7 and DUSP9. They consist of 3 exons, are cytoplasmic in their subcellular localization and preferentially recognize ERK1 and ERK2 in vitro.
• KEGG MAPK signaling pathway: DUSP1/DUSP10/DUSP14/DUSP16/DUSP2/DUSP22/DUSP3/DUSP4/DUSP5/DUSP6/DUSP7/DUSP8/DUSP9 → MAPK1/MAPK3 (protein-protein, inhibition)
• NCI Pathway Database ErbB1 downstream signaling: Erk1-2-active (MAPK3/MAPK1) → MKP3 (DUSP6) (modification, collaborate) Kim et al., Biochemistry 2003*, Amit et al., Nat Genet 2007, Muda et al., J Biol Chem 1996*, Muda et al., J Biol Chem 1996*, Camps et al., Science 1998*
  Evidence: assay, physical interaction
• NCI Pathway Database ErbB1 downstream signaling: MKP3 (DUSP6) → Erk1-2 (MAPK3/MAPK1) (modification, activates) Kim et al., Biochemistry 2003*, Amit et al., Nat Genet 2007, Muda et al., J Biol Chem 1996*, Muda et al., J Biol Chem 1996*, Camps et al., Science 1998*
  Evidence: assay, physical interaction
• NCI Pathway Database FGF signaling pathway: MKP-3 (DUSP6) → Erk1-2 (MAPK3/MAPK1) (modification, inhibits) Zhao et al., J Biol Chem 2001, Xiao et al., J Biol Chem 2002, Bryant et al., Mol Biol Cell 2005, Matsui et al., Circ Res 2011, Elfenbein et al., Science signaling 2012
  Evidence: mutant phenotype, assay
• NCI Pathway Database ErbB1 downstream signaling: Erk1-2-active (MAPK3/MAPK1) → MKP3 (DUSP6) (transcription, activates) Amit et al., Nat Genet 2007, Muda et al., J Biol Chem 1996*
  Evidence: genetic interaction
• Reactome Reaction: MAPK1 → DUSP6 (reaction) Amit et al., Nat Genet 2007
• WikiPathways MAPK Signaling Pathway: DUSP1/DUSP6/DUSP5/DUSP7/DUSP4/DUSP10 → MAPK1 (mim-inhibition)

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

• IRef Biogrid Interaction: DUSP6 — MAPK1 (direct interaction, pull down) Muda et al., J Biol Chem 1998*
• IRef Hprd Interaction: DUSP6 — MAPK1 (in vivo) Marchetti et al., Mol Cell Biol 2005*
• IRef Hprd Interaction: DUSP6 — MAPK1 (in vitro) Marchetti et al., Mol Cell Biol 2005*
• IRef Intact Interaction: DUSP6 — MAPK1 (physical association, coimmunoprecipitation) Kim et al., J Biol Chem 2003
• IRef Ophid Interaction: DUSP6 — MAPK1 (aggregation, interologs mapping) Brown et al., Bioinformatics 2005

Text-mined interactions from Literome

Reffas et al., Biochem J 2000 : Activation of mitogen activated protein kinases ( MAPKs ), their upstream activators MAPK kinases ( MAPKKs or MEKs ) and induction of MKP-1 ( CL100/3CH134 ) and MKP-3 ( Pyst1/rVH6 ) dual-specificity MAPK phosphatases ( MKPs ) were studied in the mouse embryonic stem cell line P19 during the 7 day induction of neuronal differentiation triggered by aggregation and retinoic acid
Givant-Horwitz et al., Gynecol Oncol 2004 (MAP Kinase Signaling System...) : The objective of the present study was to investigate the expression and clinical role of dual-specificity phosphatases ( DUSP ) , inhibitors of MAPK signaling, in ovarian cancer cells at this site
Furukawa et al., Oncogene 2006 (MAP Kinase Signaling System...) : DUSP6/MKP-3 , a specific inhibitor of MAPK1/ERK2 , frequently loses its expression in primary pancreatic cancer tissues ... This evidence suggests that constitutive activation of MAPK1 synergistically induced by frequent mutation of KRAS2 and the loss of function of DUSP6 plays key roles in pancreatic carcinogenesis and progression ... By profiling of gene expressions associated with downregulation of MAPK1 induced by exogenous overexpression of DUSP6 in pancreatic cancer cells, we found that AURKA/STK15, the gene encoding Aurora-A kinase, which plays key roles in cellular mitosis, was among the downregulated genes along with its related genes, which included AURKB, TPX2 and CENPA
Cui et al., Cancer Res 2006 (Breast Neoplasms) : Furthermore, PD98059 increased the levels of phosphorylated c-Jun NH ( 2 ) -terminal kinase ( JNK ) in tamoxifen treated MKP3 overexpressing cells, suggesting an interaction between MKP3 levels, activation of ERK1/2 MAPK , and JNK signaling in human breast cancer cells
Furukawa et al., Biochem Biophys Res Commun 2008 : We previously found that human pancreatic cancer cells frequently lost DUSP6 expression, which could induce constitutively active MAPK1 , and the loss was associated with hypermethylation of the CpG cluster region of intron 1 of DUSP6
Hernández-Martínez et al., Development 2009 : Inhibition of the mitogen activated protein kinase ( Mapk ) pathway prevents the survival effect of Fgf8 on interdigital cells and the accompanying Erk1/2 phosphorylation and induction of Mkp3 expression
Kumabe et al., Microbiol Immunol 2010 : Activation of MAPK is negatively regulated by DUSP , which dephosphorylate the phosphothreonine and phosphotyrosine residues
Zhang et al., J Biol Chem 2011 (MAP Kinase Signaling System) : Remarkably, MKP3, ERK2 , and phosphorylated p38a can form a stable ternary complex in solution, and the phosphatase activity of MKP3 toward p38a substrate is allosterically regulated by ERK2-MKP3 interaction
Camps et al., Science 1998 : Catalytic activation of the phosphatase MKP-3 by ERK2 mitogen activated protein kinase