mitogen activated protein kinase kinase 7


Gene Symbol: mitogen activated protein kinase kinase 7
Description: mitogen activated protein kinase kinase 7
Alias: JNKK, Jnkk2, Mapkk7, Mek7, Mkk7, dual specificity mitogen-activated protein kinase kinase 7, JNK kinase 2, JNK-activating kinase 2, JNKK 2, MAP kinase kinase 7, MAPK/ERK kinase 7, MAPKK 7, MEK 7, c-Jun N-terminal kinase kinase 2, map2k7
Species: rat

Top Publications

  1. Zhang Q, Tian H, Fu X, Zhang G. Delayed activation and regulation of MKK7 in hippocampal CA1 region following global cerebral ischemia in rats. Life Sci. 2003;74:37-45 pubmed
    ..To determine whether mitogen-activated protein kinase kinase 7 (MKK7) play a role in JNK activation in response to the stress of global cerebral ischemia, we tested the activation of ..
  2. Vander Griend D, Kocherginsky M, Hickson J, Stadler W, Lin A, Rinker Schaeffer C. Suppression of metastatic colonization by the context-dependent activation of the c-Jun NH2-terminal kinase kinases JNKK1/MKK4 and MKK7. Cancer Res. 2005;65:10984-91 pubmed
    ..1 model of spontaneous metastasis. Ectopic expression of the JNK-specific kinase MKK7 suppresses the formation of overt metastases, whereas the p38-specific kinase MKK6 has no effect...
  3. Pan J, Zhang Q, Zhang G. The neuroprotective effects of K252a through inhibiting MLK3/MKK7/JNK3 signaling pathway on ischemic brain injury in rat hippocampal CA1 region. Neuroscience. 2005;131:147-59 pubmed
    ..These results indicated that cerebral ischemia induced the continuous activation of MLK3/MKK7/JNK3 cascade, which all had two active waves only in the CA1 region...
  4. Lotan T, Lyon M, Huo D, Taxy J, Brendler C, Foster B, et al. Up-regulation of MKK4, MKK6 and MKK7 during prostate cancer progression: an important role for SAPK signalling in prostatic neoplasia. J Pathol. 2007;212:386-94 pubmed
    ..This study evaluates MKK4, MKK6 and MKK7 expression during prostate cancer progression in humans and in the transgenic adenocarcinoma of a mouse prostate (..
  5. Zeng X, Li M, Pan J, Ji T, Yang B, Zhang B, et al. Activation of c-Jun N-terminal kinase 1/2 regulated by nitric oxide is associated with neuronal survival in hippocampal neurons in a rat model of ischemia. Chin Med J (Engl). 2011;124:3367-72 pubmed
    ..Administration of 7-NI and AMT can decrease I/R-induced neuronal loss in hippocampal CA1 region. JNK1/2 activation is associated with endogenous NO in response to ischemic insult. ..
  6. Zama T, Aoki R, Kamimoto T, Inoue K, Ikeda Y, Hagiwara M. Scaffold role of a mitogen-activated protein kinase phosphatase, SKRP1, for the JNK signaling pathway. J Biol Chem. 2002;277:23919-26 pubmed
    ..protein kinase (MAPK) phosphatase (MKP) family that interacts physically with the MAPK kinase (MAPKK) MKK7, a c-Jun N-terminal kinase (JNK) activator, and inactivates the MAPK JNK pathway...
  7. Johnson G, Nakamura K. The c-jun kinase/stress-activated pathway: regulation, function and role in human disease. Biochim Biophys Acta. 2007;1773:1341-8 pubmed
    ..In this review, we present our current understanding of JNK regulation and their involvement in homeostasis and dysregulation in human disease. ..
  8. Hickson J, Huo D, Vander Griend D, Lin A, Rinker Schaeffer C, Yamada S. The p38 kinases MKK4 and MKK6 suppress metastatic colonization in human ovarian carcinoma. Cancer Res. 2006;66:2264-70 pubmed
    ..Because MKK4 can activate either of two MAPKs, p38 or JNK, we expressed MKK6 or MKK7, specific activators of these MAPKs, respectively, to delineate which MAPK signaling module was involved in MKK4-..
  9. Xu Z, Kukekov N, Greene L. POSH acts as a scaffold for a multiprotein complex that mediates JNK activation in apoptosis. EMBO J. 2003;22:252-61 pubmed
    ..Thus, POSH appears to function as a scaffold in a multiprotein complex that links activated Rac1 and downstream elements of the JNK apoptotic cascade. ..

More Information


  1. Kohlstedt K, Brandes R, Muller Esterl W, Busse R, Fleming I. Angiotensin-converting enzyme is involved in outside-in signaling in endothelial cells. Circ Res. 2004;94:60-7 pubmed
    ..Thus, ACE is involved in outside-in signaling in endothelial cells and "ACE signaling" may be an important cellular mechanism contributing to the beneficial effects of ACE inhibitors. ..
  2. Li C, Wang R, Zhang Q, Zhang G. Activated mitogen-activated protein kinase kinase 7 redistributes to the cytosol and binds to Jun N-terminal kinase-interacting protein 1 involving oxidative stress during early reperfusion in rat hippocampal CA1 region. J Neurochem. 2005;93:290-8 pubmed
    ..Our results showed that both protein expression and activation of MKK7 were increased rapidly with peaks at 10 min of reperfusion in the nucleus of the hippocampal CA1 region...
  3. Haeusgen W, Herdegen T, Waetzig V. MKK7?1 reverses nerve growth factor signals: proliferation and cell death instead of neuritogenesis and protection. Cell Signal. 2011;23:1281-90 pubmed publisher
    ..c-Jun N-terminal kinases (JNKs) are the exclusive downstream substrates of mitogen-activated protein kinase kinase 7 (MKK7)...
  4. Trotter L, Panton W, Hajimohamadreza I, Petalidis L, Ward R, Fleming Y, et al. Mitogen-activated protein kinase kinase 7 is activated during low potassium-induced apoptosis in rat cerebellar granule neurons. Neurosci Lett. 2002;320:29-32 pubmed
    ..Using an immune-complex kinase assay, we measured the activation of MKK4 and MKK7 in low potassium (LK)-induced apoptosis of rat cerebellar granule neurons (CGN)...
  5. Itoh T, Horiuchi M, Ikeda R, Xu J, Bannerman P, Pleasure D, et al. ZPK/DLK and MKK4 form the critical gateway to axotomy-induced motoneuron death in neonates. J Neurosci. 2014;34:10729-42 pubmed publisher
    ..In contrast to MKK4/MAP2K4, mice lacking MKK7/MAP2K7, another mitogen-activated protein kinase kinase directly downstream of ZPK/DLK, conditionally in neurons did not ..
  6. Waetzig V, Herdegen T. MEKK1 controls neurite regrowth after experimental injury by balancing ERK1/2 and JNK2 signaling. Mol Cell Neurosci. 2005;30:67-78 pubmed
    ..MEKK1 as an activator of both the ERK1/2 and JNK2 pathways, whereby the ERK1/2 kinase MEK1 and the JNK kinase MKK7 bind to MEKK1 in a competing fashion...
  7. Wang R, Zhang Q, Han D, Xu J, Lu Q, Zhang G. Inhibition of MLK3-MKK4/7-JNK1/2 pathway by Akt1 in exogenous estrogen-induced neuroprotection against transient global cerebral ischemia by a non-genomic mechanism in male rats. J Neurochem. 2006;99:1543-54 pubmed
    ..Our data indicate that in response to estrogen, ERalpha interacts with PI3K to activate Akt1, which may inhibit the MLK3-MKK4/7-JNK1/2 pathway to protect hippocampal CA1 neurons against global cerebral ischemia in male rats. ..
  8. Yao Z, Diener K, Wang X, Zukowski M, Matsumoto G, Zhou G, et al. Activation of stress-activated protein kinases/c-Jun N-terminal protein kinases (SAPKs/JNKs) by a novel mitogen-activated protein kinase kinase. J Biol Chem. 1997;272:32378-83 pubmed
    ..We have isolated a cDNA encoding a novel protein kinase that has significant homology to MKKs. The novel kinase MKK7 has a nucleotide sequence that encodes an open reading frame of 347 amino acids with 11 kinase subdomains...
  9. Vercelli A, Biggi S, Sclip A, Repetto I, Cimini S, Falleroni F, et al. Exploring the role of MKK7 in excitotoxicity and cerebral ischemia: a novel pharmacological strategy against brain injury. Cell Death Dis. 2015;6:e1854 pubmed publisher
    ..growth arrest and DNA damage-inducible 45β (GADD45β-I)) targeting mitogen-activated protein kinase kinase 7 (MKK7), an upstream activator of JNK, which exclusively mediates JNK's pathological activation...
  10. Harding S, Browne G, Miller B, Prigent S, Dickens M. Activation of ASK1, downstream MAPKK and MAPK isoforms during cardiac ischaemia. Biochim Biophys Acta. 2010;1802:733-40 pubmed publisher
    ..Consistent with a lack of JNK activation, we saw no activation of MKK4 or MKK7 at any time point during ischaemia...
  11. Zhang Q, Pei D, Guan Q, Sun Y, Liu X, Zhang G. Crosstalk between PSD-95 and JIP1-mediated signaling modules: the mechanism of MLK3 activation in cerebral ischemia. Biochemistry. 2007;46:4006-16 pubmed
    ..In addition, JIP1, functioning as a scaffold protein, could couple MLK3-MKK7-JNK to form a specific signaling module and facilitate the activation of the JNK signal pathway...
  12. Itoh A, Wang Z, Ito Y, Reddy U, Itoh T. SP3 acts as a positive regulator on the core promoter of human ZPK gene. Biochem Biophys Res Commun. 2004;313:612-8 pubmed
    ..Our results suggest that, for the selective expression of ZPK gene, cell-specific negative regulatory element(s) which locate outside of the core promoter region repress the potent basic promoter activity. ..
  13. Foltz I, Gerl R, Wieler J, Luckach M, Salmon R, Schrader J. Human mitogen-activated protein kinase kinase 7 (MKK7) is a highly conserved c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) activated by environmental stresses and physiological stimuli. J Biol Chem. 1998;273:9344-51 pubmed
    ..the cloning of a novel human activator of c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase kinase 7 (MKK7)...
  14. Haeusgen W, Herdegen T, Waetzig V. Specific regulation of JNK signalling by the novel rat MKK7gamma1 isoform. Cell Signal. 2010;22:1761-72 pubmed publisher
    ..In the present study we report the cloning and characterization of the novel rat MKK7gamma1, a splice variant of MKK7 with an additional exon in the N-terminal region, in the neuronal pheochromocytoma cell line PC12...
  15. Butterfield L, Zentrich E, Beekman A, Heasley L. Stress- and cell type-dependent regulation of transfected c-Jun N-terminal kinase and mitogen-activated protein kinase kinase isoforms. Biochem J. 1999;338 ( Pt 3):681-6 pubmed
    ..In addition, HA-tagged forms of the dual-specificity mitogen-activated protein kinase kinases (MKKs), MKK4 and MKK7, which are specific activators of the JNK enzymes, were similarly expressed...
  16. Tournier C, Whitmarsh A, Cavanagh J, Barrett T, Davis R. The MKK7 gene encodes a group of c-Jun NH2-terminal kinase kinases. Mol Cell Biol. 1999;19:1569-81 pubmed
    ..Two MAPKKs, MKK4 and MKK7, have been identified as JNK activators...