MKNK1

Summary

Gene Symbol: MKNK1
Description: MAP kinase interacting serine/threonine kinase 1
Alias: MNK1, MAP kinase-interacting serine/threonine-protein kinase 1, MAP kinase signal-integrating kinase 1, MAPK signal-integrating kinase 1
Species: human
Products:     MKNK1

Top Publications

  1. Dobrikov M, Dobrikova E, Shveygert M, Gromeier M. Phosphorylation of eukaryotic translation initiation factor 4G1 (eIF4G1) by protein kinase C{alpha} regulates eIF4G1 binding to Mnk1. Mol Cell Biol. 2011;31:2947-59 pubmed publisher
    ..For example, convergent MAPK signals to Mnk1 lead to phosphorylation of eukaryotic translation initiation factor 4E (eIF4E), which has been linked to malignant ..
  2. Pyronnet S, Imataka H, Gingras A, Fukunaga R, Hunter T, Sonenberg N. Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E. EMBO J. 1999;18:270-9 pubmed
    ..One strong candidate for the eIF4E kinase is the recently cloned MAPK-activated protein kinase, Mnk1, which phosphorylates eIF4E on its physiological site Ser209 in vitro...
  3. Worch J, Tickenbrock L, Schwable J, Steffen B, Cauvet T, Mlody B, et al. The serine-threonine kinase MNK1 is post-translationally stabilized by PML-RARalpha and regulates differentiation of hematopoietic cells. Oncogene. 2004;23:9162-72 pubmed
    ..The cytoplasmic serine and threonine kinase MNK1 was identified as one of the target genes...
  4. Parra J, Buxade M, Proud C. Features of the catalytic domains and C termini of the MAPK signal-integrating kinases Mnk1 and Mnk2 determine their differing activities and regulatory properties. J Biol Chem. 2005;280:37623-33 pubmed
    The MAPK signal-integrating kinases Mnk1 and Mnk2 are closely related but show marked differences in their basal activities and regulation...
  5. Lim S, Saw T, Zhang M, Janes M, Nacro K, Hill J, et al. Targeting of the MNK-eIF4E axis in blast crisis chronic myeloid leukemia inhibits leukemia stem cell function. Proc Natl Acad Sci U S A. 2013;110:E2298-307 pubmed publisher
    ..Our findings identify the MNK-eIF4E axis as a specific and critical regulator of BC self-renewal, and suggest that pharmacologic inhibition of the MNK kinases may be therapeutically useful in BC chronic myeloid leukemia...
  6. Grzmil M, Huber R, Hess D, Frank S, Hynx D, Moncayo G, et al. MNK1 pathway activity maintains protein synthesis in rapalog-treated gliomas. J Clin Invest. 2014;124:742-54 pubmed publisher
    ..Targeted depletion of MAPK-interacting Ser/Thr kinase 1 (MNK1) sensitizes glioma cells to the mTORC1 inhibitor rapamycin through an indistinct mechanism...
  7. Fukunaga R, Hunter T. MNK1, a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase substrates. EMBO J. 1997;16:1921-33 pubmed
    ..A novel clone isolated in this screen, designated MNK1, encodes a protein-serine/threonine kinase, which is most similar to MAP kinase-activated protein kinase 2 (MAPKAP-..
  8. Knauf U, Tschopp C, Gram H. Negative regulation of protein translation by mitogen-activated protein kinase-interacting kinases 1 and 2. Mol Cell Biol. 2001;21:5500-11 pubmed
    ..Here we demonstrate that phosphorylation of eIF4E via MNK1 is mediated via the activation of either the Erk or p38 pathway...
  9. Wheater M, Johnson P, Blaydes J. The role of MNK proteins and eIF4E phosphorylation in breast cancer cell proliferation and survival. Cancer Biol Ther. 2010;10:728-35 pubmed publisher

More Information

Publications116 found, 100 shown here

  1. Astanehe A, Finkbeiner M, Krzywinski M, Fotovati A, Dhillon J, Berquin I, et al. MKNK1 is a YB-1 target gene responsible for imparting trastuzumab resistance and can be blocked by RSK inhibition. Oncogene. 2012;31:4434-46 pubmed publisher
    ..b>MNK1 and MNK2 were subsequently shown to be overexpressed in the resistant cell lines; however, only the former was a YB-..
  2. Waskiewicz A, Flynn A, Proud C, Cooper J. Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2. EMBO J. 1997;16:1909-20 pubmed
    ..have identified a new subfamily of murine serine/threonine kinases, whose members, MAP kinase-interacting kinase 1 (Mnk1) and Mnk2, bind tightly to the growth factor-regulated MAP kinases, Erk1 and Erk2...
  3. Goto S, Yao Z, Proud C. The C-terminal domain of Mnk1a plays a dual role in tightly regulating its activity. Biochem J. 2009;423:279-90 pubmed publisher
    ..The MNK1 gene gives rise to two proteins, Mnk1a and Mnk1b, which possess distinct C-termini and properties...
  4. Zhang M, Jiang L, Tao J, Pan Z, He M, Su D, et al. Design, synthesis and biological evaluation of 4-aniline-thieno[2,3-d]pyrimidine derivatives as MNK1 inhibitors against renal cell carcinoma and nasopharyngeal carcinoma. Bioorg Med Chem. 2019;: pubmed publisher
    MAP Kinase Interacting Serine/Threonine Kinase 1 (MNK1) play important roles in the signaling transduction of MAPK pathways...
  5. Ramalingam S, Ramamurthy V, Gediya L, Murigi F, Purushottamachar P, Huang W, et al. The Novel Mnk1/2 Degrader and Apoptosis Inducer VNLG-152 Potently Inhibits TNBC Tumor Growth and Metastasis. Cancers (Basel). 2019;11: pubmed publisher
    ..of eukaryotic initiation factor 4E (eIF4E) by mitogen-activated protein kinase (MAPK)-interacting kinases 1 and 2 (Mnk1/2) play a critical role in the development, progression and metastasis of TNBC...
  6. Rius Pérez S, Tormos A, Pérez S, Finamor I, Rada P, Valverde A, et al. p38α deficiency restrains liver regeneration after partial hepatectomy triggering oxidative stress and liver injury. Sci Rep. 2019;9:3775 pubmed publisher
    ..hepatocytes showed enhanced binucleation and increased levels of phospho-histone H3 but impaired phosphorylation of MNK1 after hepatectomy...
  7. Badarau A, Dennison C. Copper trafficking mechanism of CXXC-containing domains: insight from the pH-dependence of their Cu(I) affinities. J Am Chem Soc. 2011;133:2983-8 pubmed publisher
    ..have investigated the influence of pH on copper trafficking between HAH1 and the first MBD of the Menkes protein (MNK1). Cu(I) affinities of 5.6 × 10(17) and 3.6 × 10(17) M(-1) have been determined at pH 7...
  8. Riis J, Johansen C, Vestergaard C, Otkjaer K, Kragballe K, Iversen L. CCL27 expression is regulated by both p38 MAPK and IKKβ signalling pathways. Cytokine. 2011;56:699-707 pubmed publisher
    ..of mitogen- and stress-activated kinase 1 (MSK1) or the mitogen-activated protein kinase-interacting kinases (Mnk1+2), downstream kinases of p38 MAPK, on IL-1β-induced CCL27 expression in NHEK were investigated...
  9. Rosina E, Battan B, Siracusano M, Di Criscio L, Hollis F, Pacini L, et al. Disruption of mTOR and MAPK pathways correlates with severity in idiopathic autism. Transl Psychiatry. 2019;9:50 pubmed publisher
    ..Specifically, rpS6, p-eIF4E, TSC1 and p-MNK1 expression discriminated patients according to their clinical diagnosis, suggesting that components of protein ..
  10. Kumar R, Khandelwal N, Chander Y, Riyesh T, Tripathi B, Kashyap S, et al. MNK1 inhibitor as an antiviral agent suppresses buffalopox virus protein synthesis. Antiviral Res. 2018;160:126-136 pubmed publisher
    A small molecule chemical inhibitor CGP57380 that blocks activation of MAPK interacting kinase 1 (MNK1) was found to significantly suppress buffalopox virus (BPXV) replication. BPXV infection was shown to induce MNK1 activation...
  11. Guo Q, Li V, Nichol J, Huang F, Yang W, Preston S, et al. MNK1/NODAL Signaling Promotes Invasive Progression of Breast Ductal Carcinoma In Situ. Cancer Res. 2019;79:1646-1657 pubmed publisher
    ..MAPK-interacting serine/threonine-protein kinase 1 (MNK1) signaling can promote cell invasion...
  12. Ear T, Tatsiy O, Allard F, McDonald P. Regulation of Discrete Functional Responses by Syk and Src Family Tyrosine Kinases in Human Neutrophils. J Immunol Res. 2017;2017:4347121 pubmed publisher
    ..g., eIF-4E, S6K, and MNK1) involved in translational control. By contrast, delayed apoptosis appears to be independent of either STKs or Syk...
  13. Joshi S, Platanias L. Mnk kinase pathway: Cellular functions and biological outcomes. World J Biol Chem. 2014;5:321-33 pubmed publisher
    The mitogen-activated protein kinase (MAPK) interacting protein kinases 1 and 2 (Mnk1 and Mnk2) play important roles in controlling signals involved in mRNA translation...
  14. Moens U, Kostenko S. Structure and function of MK5/PRAK: the loner among the mitogen-activated protein kinase-activated protein kinases. Biol Chem. 2013;394:1115-32 pubmed publisher
    ..identified, and they are divided into five subgroups: the ribosomal-S6-kinases RSK1-4, the MAPK-interacting kinases MNK1 and 2, the mitogen- and stress-activated kinases MSK1 and 2, the MAPK-activated protein kinases MK2 and 3, and the ..
  15. Eckerdt F, Beauchamp E, Bell J, Iqbal A, Su B, Fukunaga R, et al. Regulatory effects of a Mnk2-eIF4E feedback loop during mTORC1 targeting of human medulloblastoma cells. Oncotarget. 2014;5:8442-51 pubmed
    ..This eIF4E phosphorylation is Mnk2- mediated, but Mnk1-independent, and acts as a survival mechanism for medulloblastoma cells...
  16. Roth H, Magg V, Uch F, Mutz P, Klein P, Haneke K, et al. Flavivirus Infection Uncouples Translation Suppression from Cellular Stress Responses. MBio. 2017;8: pubmed publisher
    ..Rather, DENV infection induced p38-Mnk1 signaling that resulted in the phosphorylation of the eukaryotic translation initiation factor eIF4E and was ..
  17. Kostenko S, Shiryaev A, Dumitriu G, Gerits N, Moens U. Cross-talk between protein kinase A and the MAPK-activated protein kinases RSK1 and MK5. J Recept Signal Transduct Res. 2011;31:1-9 pubmed publisher
    ..The MAPKAPK family includes the ribosomal-S6-kinases (RSK1-4), the MAPK-interacting kinases (MNK1 and 2), the mitogen-and stress-activated kinases (MSK1 and 2), and the MAPKAPK (MK2, 3, and 5) subfamilies...
  18. Huang X, Yang C, Han Q, Ye X, Lei W, Qian W. MNK1 inhibitor CGP57380 overcomes mTOR inhibitor-induced activation of eIF4E: the mechanism of synergic killing of human T-ALL cells. Acta Pharmacol Sin. 2018;39:1894-1901 pubmed publisher
    ..Then we examined the antileukemia effects of CGP57380, a MNK1 inhibitor, and we found that CGP57380 (4-16 μM) dose-dependently suppressed the expression of both phosphor-MNK1 ..
  19. Pham T, Kumar K, DeCant B, Shang M, Munshi S, Matsangou M, et al. Induction of MNK Kinase-dependent eIF4E Phosphorylation by Inhibitors Targeting BET Proteins Limits Efficacy of BET Inhibitors. Mol Cancer Ther. 2019;18:235-244 pubmed publisher
    ..Significantly, MNK inhibitors and MNK1/2 knockdown enhanced the efficacy of BETis in suppressing proliferation of cancer cells in vitro and in a ..
  20. Jin X, Merrett J, Tong S, Flower B, Xie J, Yu R, et al. Design, synthesis and activity of Mnk1 and Mnk2 selective inhibitors containing thieno[2,3-d]pyrimidine scaffold. Eur J Med Chem. 2019;162:735-751 pubmed publisher
    The mitogen-activated protein kinase-interacting kinases 1 and 2 (MNK1 and MNK2) phosphorylate eukaryotic initiation factor 4E (eIF4E) and play important roles in promoting tumorigenesis and metabolic disease...
  21. Shi Y, Yang Y, Hoang B, Bardeleben C, Holmes B, Gera J, et al. Therapeutic potential of targeting IRES-dependent c-myc translation in multiple myeloma cells during ER stress. Oncogene. 2016;35:1015-24 pubmed publisher
    ..IRES activity was dependent on upstream MAPK (mitogen-activated protein kinase) and MNK1 (MAPK-interacting serine/threonine kinase 1) signaling...
  22. Kumar R, Khandelwal N, Thachamvally R, Tripathi B, Barua S, Kashyap S, et al. Role of MAPK/MNK1 signaling in virus replication. Virus Res. 2018;253:48-61 pubmed publisher
    ..MAPK interacting kinase 1 (MNK1) has been shown to regulate both cap-dependent and internal ribosomal entry sites (IRES)-mediated mRNA translation...
  23. Schumann M, Dobbelstein M. Adenovirus-induced extracellular signal-regulated kinase phosphorylation during the late phase of infection enhances viral protein levels and virus progeny. Cancer Res. 2006;66:1282-8 pubmed
    ..and mRNA levels only weakly but strongly reduced the amount of viral proteins, independently of the kinases MNK1 and PKR...
  24. Gaestel M, Mengel A, Bothe U, Asadullah K. Protein kinases as small molecule inhibitor targets in inflammation. Curr Med Chem. 2007;14:2214-34 pubmed
    ..IKKs), against MAPK kinases (MEKs, MKKs), against MAPKs (ERK2, p38, JNKs) and against their downstream kinases MNK1 and MK2/3...
  25. Martínez A, Sesé M, Losa J, Robichaud N, Sonenberg N, Aasen T, et al. Phosphorylation of eIF4E Confers Resistance to Cellular Stress and DNA-Damaging Agents through an Interaction with 4E-T: A Rationale for Novel Therapeutic Approaches. PLoS ONE. 2015;10:e0123352 pubmed publisher
    ..Cancer cells treated with the Mnk1/2 inhibitor CGP57380 to prevent eIF4E phosphorylation and mouse embryonic fibroblasts derived from Mnk1/2 knockout ..
  26. Aguilar Valles A, Haji N, De Gregorio D, Matta Camacho E, Eslamizade M, Popic J, et al. Translational control of depression-like behavior via phosphorylation of eukaryotic translation initiation factor 4E. Nat Commun. 2018;9:2459 pubmed publisher
    ..We investigated the involvement of MNK1/2 (MAPK-interacting serine/threonine-protein kinase 1 and 2) and their target, eIF4E (eukaryotic initiation factor ..
  27. Li C, He J, Chen J, Zhao J, Gu D, Hixson J, et al. Genome-Wide Gene-Sodium Interaction Analyses on Blood Pressure: The Genetic Epidemiology Network of Salt-Sensitivity Study. Hypertension. 2016;68:348-55 pubmed publisher
    ..11×10(-22)) and mean arterial pressure (P=2.86×10(-15)). Genome-wide gene-based analysis identified MKNK1 (P=6.70×10(-7)), C2orf80 (P<1.00×10(-12)), EPHA6 (P=2.88×10(-7)), SCOC-AS1 (P=4.35×10(-14)), SCOC (P=6...
  28. Liong S, Lappas M. Markers of protein synthesis are increased in fetal membranes and myometrium after human labour and delivery. Reprod Fertil Dev. 2018;30:313-329 pubmed publisher
    ..eukaryotic elongation factor 2 kinase (EEF2K), mitogen-activated protein kinase interacting protein kinase 1 (MKNK1) and eukaryotic translation initiation factor 4E (EIF4E), and their role in regulating inflammation in human ..
  29. Wang S, Li B, Liu B, Huang M, Li D, Guan L, et al. Design and synthesis of novel 6-hydroxy-4-methoxy-3-methylbenzofuran-7-carboxamide derivatives as potent Mnks inhibitors by fragment-based drug design. Bioorg Med Chem. 2018;26:4602-4614 pubmed publisher
    ..45, 1.16, 3.55 and 0.27 μM, respectively. And these compounds inhibited the activity of Mnk1 at the same time...
  30. Figueiredo V, Caldow M, Massie V, Markworth J, Cameron Smith D, Blazevich A. Ribosome biogenesis adaptation in resistance training-induced human skeletal muscle hypertrophy. Am J Physiol Endocrinol Metab. 2015;309:E72-83 pubmed publisher
    ..activation of the ERK and mTOR pathways were similar before and after RT, as assessed by phosphorylation of ERK, MNK1, p70S6K, and S6 ribosomal protein 1 h postexercise...
  31. Han J, Song J, Li X, Zhu M, Guo W, Xing W, et al. Ligustrazine Suppresses the Growth of HRPC Cells through the Inhibition of Cap- Dependent Translation Via Both the mTOR and the MEK/ERK Pathways. Anticancer Agents Med Chem. 2015;15:764-72 pubmed
    ..In addition, the transient overexpression of eIF4E or MNK1 prevents the Ligustrazine-induced inhibition of proliferation and confers significant protection against ..
  32. Müller D, Martineau Y, Bousquet C, Pyronnet S. Imbalanced splicing in MAPK signaling sustains Ras-induced transformation. Clin Res Hepatol Gastroenterol. 2015;39:155-6 pubmed publisher
    ..The eIF4E factor is phosphorylated by MAPK-interacting protein kinases 1 and 2 (MNK1 and MNK2). Due to alternative splicing, two MNK2 proteins exist (MNK2a and MNK2b)...
  33. Beggs J, Tian S, Jones G, Xie J, Iadevaia V, Jenei V, et al. The MAP kinase-interacting kinases regulate cell migration, vimentin expression and eIF4E/CYFIP1 binding. Biochem J. 2015;467:63-76 pubmed publisher
    The MAP kinase-interacting kinases (Mnk1 and Mnk2) are activated by ERK and are best known for phosphorylating the translation initiation factor eIF4E...
  34. Genheden M, Kenney J, Johnston H, Manousopoulou A, Garbis S, Proud C. BDNF stimulation of protein synthesis in cortical neurons requires the MAP kinase-interacting kinase MNK1. J Neurosci. 2015;35:972-84 pubmed publisher
    ..we show that BDNF-induced upregulation of protein synthesis requires MEK/ERK signaling and the downstream kinase, MNK1, which phosphorylates eukaryotic initiation factor (eIF) 4E...
  35. Moore C, Pickford J, Cagampang F, Stead R, Tian S, Zhao X, et al. MNK1 and MNK2 mediate adverse effects of high-fat feeding in distinct ways. Sci Rep. 2016;6:23476 pubmed publisher
    The MAP kinase-interacting kinases (MNK1 and MNK2) are non-essential enzymes which are activated by MAP kinases. They are implicated in controlling protein synthesis...
  36. D Abronzo L, Ghosh P. eIF4E Phosphorylation in Prostate Cancer. Neoplasia. 2018;20:563-573 pubmed publisher
    ..mTOR) activation and is phosphorylated by the mitogen-activated protein kinase (MAPK) interacting protein kinases (Mnk1/2)...
  37. Marcus H, Attar Schneider O, Dabbah M, Zismanov V, Tartakover Matalon S, Lishner M, et al. Mesenchymal stem cells secretomes' affect multiple myeloma translation initiation. Cell Signal. 2016;28:620-30 pubmed publisher
    ..cell count, cell death, proliferation, cell cycle, autophagy) and TI (factors: eIF4E, teIF4GI; regulators: mTOR, MNK1/2, 4EBP; targets: cyclin D1, NFκB, SMAD5, cMyc, HIF1α)...
  38. Sansook S, Lineham E, Hassell Hart S, Tizzard G, Coles S, Spencer J, et al. Probing the Anticancer Action of Novel Ferrocene Analogues of MNK Inhibitors. Molecules. 2018;23: pubmed publisher
    Two novel ferrocene-containing compounds based upon a known MNK1/2 kinase (MAPK-interacting kinase) inhibitor have been synthesized...
  39. O Loghlen A, González V, Jurado T, Salinas M, Martín M. Characterization of the activity of human MAP kinase-interacting kinase Mnk1b. Biochim Biophys Acta. 2007;1773:1416-27 pubmed
    ..Identification and molecular characterization of Mnk1b, a splice variant of human MAP kinase-interacting kinase Mnk1, Exp. Cell Res. 299 (2004) 343-355]. Mnk1b has much higher basal eIF4E kinase activity than Mnk1a...
  40. Lupberger J, Casanova C, Fischer B, Weiss A, Fofana I, Fontaine N, et al. PI4K-beta and MKNK1 are regulators of hepatitis C virus IRES-dependent translation. Sci Rep. 2015;5:13344 pubmed publisher
    ..We demonstrate that the HCV host cell cofactors PI4K and MKNK1 are positive regulators of HCV IRES translation representing a novel pathway with a functional relevance for the ..
  41. Makanae Y, Ogasawara R, Sato K, Takamura Y, Matsutani K, Kido K, et al. Acute bout of resistance exercise increases vitamin D receptor protein expression in rat skeletal muscle. Exp Physiol. 2015;100:1168-76 pubmed publisher
    ..05), and the resistance exercise significantly increased phosphorylated ERK1/2 and Mnk1 expression (P < 0.05), which may be associated with VDR expression, immediately after exercise...
  42. Teo T, Lam F, Yu M, Yang Y, Basnet S, Albrecht H, et al. Pharmacologic Inhibition of MNKs in Acute Myeloid Leukemia. Mol Pharmacol. 2015;88:380-9 pubmed publisher
    ..Herein, a potent and selective Mnk2 inhibitor (MNKI-85) and a dual-specific Mnk1 and Mnk2 inhibitor (MNKI-19), both derived from a thienopyrimidinyl chemotype, were selected to explore their ..
  43. Zhou X, Xu L, Wang Y, Wang W, Sprengers D, Metselaar H, et al. Requirement of the eukaryotic translation initiation factor 4F complex in hepatitis E virus replication. Antiviral Res. 2015;124:11-9 pubmed publisher
    ..Notably, phosphorylation of eIF4E induced by MNK1/2 activation is not involved in HEV replication...
  44. Figueiredo V, Roberts L, Markworth J, Barnett M, Coombes J, Raastad T, et al. Impact of resistance exercise on ribosome biogenesis is acutely regulated by post-exercise recovery strategies. Physiol Rep. 2016;4: pubmed publisher
    ..RE increased the phosphorylation of the p38-MNK1-eIF4E axis, an effect only evident with ACT recovery...
  45. Moy J, Khoutorsky A, Asiedu M, Black B, Kuhn J, Barragán Iglesias P, et al. The MNK-eIF4E Signaling Axis Contributes to Injury-Induced Nociceptive Plasticity and the Development of Chronic Pain. J Neurosci. 2017;37:7481-7499 pubmed publisher
    ..These effects were recapitulated in Mnk1/2-/- mice and with the MNK1/2 inhibitor cercosporamide...
  46. Hsu K, Guan B, Cheng X, Guan D, Lam M, Hatzoglou M, et al. Translational control of PML contributes to TNFα-induced apoptosis of MCF7 breast cancer cells and decreased angiogenesis in HUVECs. Cell Death Differ. 2016;23:469-83 pubmed publisher
    ..of PML gene regulation in which the p38 MAPK and its downstream kinase MAP kinase-activated protein kinase 1 (MNK1) mediate TNFα-induced PML protein accumulation and PML NB formation...
  47. Hussein N, Delaney T, Tounsel B, Liebl F. The Extracellular-Regulated Kinase Effector Lk6 is Required for Glutamate Receptor Localization at the Drosophila Neuromuscular Junction. J Exp Neurosci. 2016;10:77-91 pubmed publisher
    ..Our data show that Lk6, the Drosophila homolog of Mnk1 and Mnk2, is required in either presynaptic neurons or postsynaptic muscle for the proper localization of the ..
  48. Wen Q, Wang W, Luo J, Chu S, Chen L, Xu L, et al. CGP57380 enhances efficacy of RAD001 in non-small cell lung cancer through abrogating mTOR inhibition-induced phosphorylation of eIF4E and activating mitochondrial apoptotic pathway. Oncotarget. 2016;7:27787-801 pubmed publisher
    ..Here, our results showed that over-expression of p-Mnk1 and p-eIF4E was significantly associated with poor overall survival of NSCLC patients and high expression of p-Mnk1 ..
  49. Kościuczuk E, Saleiro D, Kroczynska B, Beauchamp E, Eckerdt F, Blyth G, et al. Merestinib blocks Mnk kinase activity in acute myeloid leukemia progenitors and exhibits antileukemic effects in vitro and in vivo. Blood. 2016;128:410-4 pubmed publisher
    ..Inhibiting Mnk1/2-induced phosphorylation of eIF4E may represent a unique approach for the treatment of AML...
  50. Yuan Y, Yan L, Wu Q, Zhou H, Jin Y, Bian Z, et al. Mnk1 (Mitogen-Activated Protein Kinase-Interacting Kinase 1) Deficiency Aggravates Cardiac Remodeling in Mice. Hypertension. 2016;68:1393-1399 pubmed
    ..Here, the role of Mnk1 (mitogen-activated protein kinase-interacting kinase 1) in cardiac remodeling was clarified...
  51. Hou S, Du P, Wang P, Wang C, Liu P, Liu H. Significance of MNK1 in prognostic prediction and chemotherapy development of epithelial ovarian cancer. Clin Transl Oncol. 2017;19:1107-1116 pubmed publisher
    ..was used to explore the expression pattern of mitogen-activated protein kinase (MAPK)-interacting kinase 1 (MNK1) in tumor tissues from 138 epithelial ovarian cancer (EOC) patients...
  52. Basnet S, Diab S, Schmid R, Yu M, Yang Y, Gillam T, et al. Identification of a Highly Conserved Allosteric Binding Site on Mnk1 and Mnk2. Mol Pharmacol. 2015;88:935-48 pubmed publisher
    ..A selection of 66 compounds was tested for Mnk1 and Mnk2 inhibition, and 9 out of 20 active compounds showed type III interaction with an allosteric site of the ..
  53. Santag S, Siegel F, Wengner A, Lange C, Bömer U, Eis K, et al. BAY 1143269, a novel MNK1 inhibitor, targets oncogenic protein expression and shows potent anti-tumor activity. Cancer Lett. 2017;390:21-29 pubmed publisher
    ..eukaryotic translation initiation factor 4E (eIF4E) is the major substrate of MAP kinase-interacting kinase 1 (MNK1), and it is located at the junction of the cancer-associated PI3K and MAPK pathways...
  54. Bell J, Eckerdt F, Alley K, Magnusson L, Hussain H, Bi Y, et al. MNK Inhibition Disrupts Mesenchymal Glioma Stem Cells and Prolongs Survival in a Mouse Model of Glioblastoma. Mol Cancer Res. 2016;14:984-993 pubmed
    ..Isoform-level subtyping using The Cancer Genome Atlas revealed that both MNK genes (MKNK1 and MKNK2) are upregulated in mesenchymal glioblastoma multiforme as compared with other subtypes...
  55. Jain S, Wang X, Chang C, Ibarra Drendall C, Wang H, Zhang Q, et al. Src Inhibition Blocks c-Myc Translation and Glucose Metabolism to Prevent the Development of Breast Cancer. Cancer Res. 2015;75:4863-75 pubmed publisher
    ..investigations revealed that Src blockade reduced glucose metabolism as a result of an inhibition in ERK1/2-MNK1-eIF4E-mediated cap-dependent translation of c-Myc and transcription of the glucose transporter GLUT1, thereby ..
  56. Geter P, Ernlund A, Bakogianni S, Alard A, Arju R, Giashuddin S, et al. Hyperactive mTOR and MNK1 phosphorylation of eIF4E confer tamoxifen resistance and estrogen independence through selective mRNA translation reprogramming. Genes Dev. 2017;31:2235-2249 pubmed publisher
    ..Resensitization to tamoxifen is restored only by reducing eIF4E expression or mTOR activity and also blocking MNK1 phosphorylation of eIF4E...
  57. Yu Y, Tian L, Feng X, Cheng J, Gong Y, Liu X, et al. eIF4E-phosphorylation-mediated Sox2 upregulation promotes pancreatic tumor cell repopulation after irradiation. Cancer Lett. 2016;375:31-38 pubmed publisher
    ..Furthermore, we identified activated eIF4E, which is phosphorylated by MNK1, as a regulator of Sox2 expression after irradiation, and pharmacologic inhibition of eIF4E with CGP57380 and ..
  58. Tanoue T, Maeda R, Adachi M, Nishida E. Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions. EMBO J. 2001;20:466-79 pubmed
  59. Grund E, Spyropoulos D, Watson D, Muise Helmericks R. Interleukins 2 and 15 regulate Ets1 expression via ERK1/2 and MNK1 in human natural killer cells. J Biol Chem. 2005;280:4772-8 pubmed
    ..Expression of a dominant negative form of MNK1, a regulator of the translation initiation factor eIF4E, blocks the expression of Ets1 as do the dominant negative ..
  60. Zhan Y, Guo J, Yang W, Goncalves C, Rzymski T, Dreas A, et al. MNK1/2 inhibition limits oncogenicity and metastasis of KIT-mutant melanoma. J Clin Invest. 2017;127:4179-4192 pubmed publisher
    ..We determined that C-KIT stimulates MAP kinase-interacting serine/threonine kinases 1 and 2 (MNK1/2), which phosphorylate eukaryotic translation initiation factor 4E (eIF4E) and render it oncogenic...
  61. de Carvalho M, McCormack A, Olson E, Ghomashchi F, Gelb M, Yates J, et al. Identification of phosphorylation sites of human 85-kDa cytosolic phospholipase A2 expressed in insect cells and present in human monocytes. J Biol Chem. 1996;271:6987-97 pubmed
    ..The results also suggest that phosphorylation of the cPLA2 by protein kinases other than mitogen-activated protein kinase may be important for the regulation of arachidonic acid release. ..
  62. Hefner Y, Borsch Haubold A, Murakami M, Wilde J, Pasquet S, Schieltz D, et al. Serine 727 phosphorylation and activation of cytosolic phospholipase A2 by MNK1-related protein kinases. J Biol Chem. 2000;275:37542-51 pubmed
    ..The p38-activated protein kinases MNK1, MSK1, and PRAK1 phosphorylate cPLA2 in vitro uniquely on Ser-727 as shown by mass spectrometry...
  63. Zheng J, Li J, Xu L, Xie G, Wen Q, Luo J, et al. Phosphorylated Mnk1 and eIF4E are associated with lymph node metastasis and poor prognosis of nasopharyngeal carcinoma. PLoS ONE. 2014;9:e89220 pubmed publisher
    ..However, whether the alterations of the expression of p-eIF4E and p-Mnk1 protein are associated with clinicopathologic/prognostic implication for NPC has not been reported...
  64. Brown M, Dobrikov M, Gromeier M. Mitogen-activated protein kinase-interacting kinase regulates mTOR/AKT signaling and controls the serine/arginine-rich protein kinase-responsive type 1 internal ribosome entry site-mediated translation and viral oncolysis. J Virol. 2014;88:13149-60 pubmed publisher
  65. Korneeva N, Song A, Gram H, Edens M, Rhoads R. Inhibition of Mitogen-activated Protein Kinase (MAPK)-interacting Kinase (MNK) Preferentially Affects Translation of mRNAs Containing Both a 5'-Terminal Cap and Hairpin. J Biol Chem. 2016;291:3455-67 pubmed publisher
    The MAPK-interacting kinases 1 and 2 (MNK1 and MNK2) are activated by extracellular signal-regulated kinases 1 and 2 (ERK1/2) or p38 in response to cellular stress and extracellular stimuli that include growth factors, cytokines, and ..
  66. Grzmil M, Seebacher J, Hess D, Behe M, Schibli R, Moncayo G, et al. Inhibition of MNK pathways enhances cancer cell response to chemotherapy with temozolomide and targeted radionuclide therapy. Cell Signal. 2016;28:1412-21 pubmed publisher
    ..Depletion of MNK activity by using two MNK inhibitors, CGP57380 or cercosporamide, as well as by MNK1-specific knockdown sensitized glioblastoma (GBM) cells and GBM-derived spheres to TMZ...
  67. O Loghlen A, González V, Piñeiro D, Pérez Morgado M, Salinas M, Martín M. Identification and molecular characterization of Mnk1b, a splice variant of human MAP kinase-interacting kinase Mnk1. Exp Cell Res. 2004;299:343-55 pubmed
    In this paper, we report the identification and molecular characterization of a splice variant of human Mnk1 which has been named as Mnk1b...
  68. Chang S, Yu K, Lee Y, An G, Beck G, Colburn N, et al. Elevated inorganic phosphate stimulates Akt-ERK1/2-Mnk1 signaling in human lung cells. Am J Respir Cell Mol Biol. 2006;35:528-39 pubmed
    ..Here, we report that Pi controls cell growth by activating ERK cascades and by facilitating the translocation of Mnk1 from cytosol into nucleus through an Akt-mediated MEK pathway...
  69. Coulthard L, Taylor J, Eyre S, Robinson J, Wilson A, Isaacs J, et al. Genetic variants within the MAP kinase signalling network and anti-TNF treatment response in rheumatoid arthritis patients. Ann Rheum Dis. 2011;70:98-103 pubmed publisher
    ..Validation of these findings in independent cohorts is warranted. ..
  70. Marzec M, Liu X, Wysocka M, Rook A, Odum N, Wasik M. Simultaneous inhibition of mTOR-containing complex 1 (mTORC1) and MNK induces apoptosis of cutaneous T-cell lymphoma (CTCL) cells. PLoS ONE. 2011;6:e24849 pubmed publisher
    ..b>MNK1 and MNK2 kinases phosphorylate and augment activity of eIF4E...
  71. Ziaei S, Shimada N, Kucharavy H, Hubbard K. MNK1 expression increases during cellular senescence and modulates the subcellular localization of hnRNP A1. Exp Cell Res. 2012;318:500-8 pubmed publisher
    ..In this study, we have explored the possible involvement of MNK1, one of the downstream effector of p38 MAPK, in the regulation of hnRNP A1...
  72. Mehrotra S, Sharma B, Joshi S, Kroczynska B, Majchrzak B, Stein B, et al. Essential role for the Mnk pathway in the inhibitory effects of type I interferons on myeloproliferative neoplasm (MPN) precursors. J Biol Chem. 2013;288:23814-22 pubmed publisher
    ..Altogether, these findings provide evidence for key and essential roles of the Mnk kinase pathway in the generation of the antineoplastic effects of type I IFNs in Jak2V617F-dependent MPNs. ..
  73. Kwegyir Afful A, Bruno R, Purushottamachar P, Murigi F, Njar V. Galeterone and VNPT55 disrupt Mnk-eIF4E to inhibit prostate cancer cell migration and invasion. FEBS J. 2016;283:3898-3918 pubmed publisher
    ..Our results suggest that gal/VNPT55 could become promising agents for the prevention and/or treatment of all stages of prostate cancer. ..
  74. Scheper G, Morrice N, Kleijn M, Proud C. The mitogen-activated protein kinase signal-integrating kinase Mnk2 is a eukaryotic initiation factor 4E kinase with high levels of basal activity in mammalian cells. Mol Cell Biol. 2001;21:743-54 pubmed
    ..In contrast to that of Mnk1, the activity of overexpressed Mnk2 is high under control conditions and could only be reduced substantially by a ..
  75. DaSilva J, Xu L, Kim H, Miller W, Bar Sagi D. Regulation of sprouty stability by Mnk1-dependent phosphorylation. Mol Cell Biol. 2006;26:1898-907 pubmed
    ..Here we identify mitogen-activated protein kinase-interacting kinase 1 (Mnk1) as the kinase that phosphorylates human Spry2 (hSpry2) on serines 112 and 121...
  76. Landon A, Muniandy P, Shetty A, Lehrmann E, Volpon L, Houng S, et al. MNKs act as a regulatory switch for eIF4E1 and eIF4E3 driven mRNA translation in DLBCL. Nat Commun. 2014;5:5413 pubmed publisher
    The phosphorylation of eIF4E1 at serine 209 by MNK1 or MNK2 has been shown to initiate oncogenic mRNA translation, a process that favours cancer development and maintenance...
  77. Ramamurthy V, Ramalingam S, Gediya L, Kwegyir Afful A, Njar V. Simultaneous targeting of androgen receptor (AR) and MAPK-interacting kinases (MNKs) by novel retinamides inhibits growth of human prostate cancer cell lines. Oncotarget. 2015;6:3195-210 pubmed
  78. Dreas A, Mikulski M, Milik M, Fabritius C, Brzózka K, Rzymski T. Mitogen-activated Protein Kinase (MAPK) Interacting Kinases 1 and 2 (MNK1 and MNK2) as Targets for Cancer Therapy: Recent Progress in the Development of MNK Inhibitors. Curr Med Chem. 2017;24:3025-3053 pubmed publisher
    MAP kinase-interacting kinases (MNK1 and MNK2) are often activated downstream of ERK and p38 MAPK in the MAP kinase family...
  79. Kim S, Ishida H, Yamane D, Yi M, Swinney D, Foung S, et al. Contrasting roles of mitogen-activated protein kinases in cellular entry and replication of hepatitis C virus: MKNK1 facilitates cell entry. J Virol. 2013;87:4214-24 pubmed publisher
    ..a role for a mitogen-activated protein kinase (MAPK)-related kinase, MAPK interacting serine/threonine kinase 1 (MKNK1), in viral entry...
  80. Zhu X, Dahlmans V, Thali R, Preisinger C, Viollet B, Voncken J, et al. AMP-activated Protein Kinase Up-regulates Mitogen-activated Protein (MAP) Kinase-interacting Serine/Threonine Kinase 1a-dependent Phosphorylation of Eukaryotic Translation Initiation Factor 4E. J Biol Chem. 2016;291:17020-7 pubmed publisher
    ..Our data suggest a physiological role for MNK1a-Ser(353) phosphorylation in regulation of the MNK1a kinase, which correlates with increased eIF4E phosphorylation in vitro and in vivo. ..
  81. Seidel P, Sun Q, Costa L, Lardinois D, Tamm M, Roth M. The MNK-1/eIF4E pathway as a new therapeutic pathway to target inflammation and remodelling in asthma. Cell Signal. 2016;28:1555-62 pubmed publisher
    ..Therefore we suggest that MNK-1 inhibition may present a new target to limit inflammation and remodelling in asthmatic airways. ..
  82. Tian S, Wang X, Proud C. Oncogenic MNK signalling regulates the metastasis suppressor NDRG1. Oncotarget. 2017;8:46121-46135 pubmed publisher
    ..MNK inhibition also decreases the phosphorylation of NDRG1. Phosphorylation of NDRG1 is reduced in cells lacking MNK1, but not MNK2-knockout cells, indicating that NDRG1 phosphorylation is a specific target for MNK1...
  83. Bell J, Eckerdt F, Dhruv H, Finlay D, Peng S, Kim S, et al. Differential Response of Glioma Stem Cells to Arsenic Trioxide Therapy Is Regulated by MNK1 and mRNA Translation. Mol Cancer Res. 2018;16:32-46 pubmed publisher
    ..As ATO has been shown to activate the MAPK-interacting kinase 1 (MNK1)-eukaryotic translation initiation factor 4E (eIF4E) pathway and subsequent mRNA translation in a negative ..
  84. Orton K, Ling J, Waskiewicz A, Cooper J, Merrick W, Korneeva N, et al. Phosphorylation of Mnk1 by caspase-activated Pak2/gamma-PAK inhibits phosphorylation and interaction of eIF4G with Mnk. J Biol Chem. 2004;279:38649-57 pubmed
    The mitogen-activated protein kinase-interacting kinase 1 (Mnk1) is phosphorylated by caspase-cleaved protein kinase Pak2/gamma-PAK but not by Cdc42-activated Pak2...
  85. Joshi S, Sharma B, Kaur S, Majchrzak B, Ueda T, Fukunaga R, et al. Essential role for Mnk kinases in type II interferon (IFNgamma) signaling and its suppressive effects on normal hematopoiesis. J Biol Chem. 2011;286:6017-26 pubmed publisher
    ..We examined the role of Mnk1 (MAPK-interacting protein kinase 1) in IFN? signaling...
  86. Brown M, Bryant J, Dobrikova E, Shveygert M, Bradrick S, Chandramohan V, et al. Induction of viral, 7-methyl-guanosine cap-independent translation and oncolysis by mitogen-activated protein kinase-interacting kinase-mediated effects on the serine/arginine-rich protein kinase. J Virol. 2014;88:13135-48 pubmed publisher
    ..In this study, we unraveled signaling pathways centered on the ERK1/2 and p38α MAPK-interacting kinases MNK1/2 and their role in controlling 7-methyl-guanosine (m(7)G) "cap"-independent translation at enterovirus type 1 ..
  87. Teo T, Yu M, Yang Y, Gillam T, Lam F, Sykes M, et al. Pharmacologic co-inhibition of Mnks and mTORC1 synergistically suppresses proliferation and perturbs cell cycle progression in blast crisis-chronic myeloid leukemia cells. Cancer Lett. 2015;357:612-23 pubmed publisher
    ..Herein, a dual-specific Mnk1/2 inhibitor MNKI-57 and a potent Mnk2-specific inhibitor MNKI-4 were selected for a panel screen against 28 human ..
  88. Fan W, Wang W, Mao X, Chu S, Feng J, Xiao D, et al. Elevated levels of p-Mnk1, p-eIF4E and p-p70S6K proteins are associated with tumor recurrence and poor prognosis in astrocytomas. J Neurooncol. 2017;131:485-493 pubmed publisher
    ..We examined and analyzed the correlation between expression of p-Mnk1, p-eIF4E and p-p70S6K proteins and clinicopathological features in 103 astrocytomas and 54 non-tumorous brain ..
  89. Berger M, Stintzing S, Heinemann V, Yang D, Cao S, Sunakawa Y, et al. Impact of genetic variations in the MAPK signaling pathway on outcome in metastatic colorectal cancer patients treated with first-line FOLFIRI and bevacizumab: data from FIRE-3 and TRIBE trials. Ann Oncol. 2017;28:2780-2785 pubmed publisher
    The MAPK-interacting kinase 1 (MKNK1) is localized downstream of the RAS/RAF/ERK and the MAP3K1/MKK/p38 signaling pathway...
  90. Cuesta R, Xi Q, Schneider R. Structural basis for competitive inhibition of eIF4G-Mnk1 interaction by the adenovirus 100-kilodalton protein. J Virol. 2004;78:7707-16 pubmed
    ..Among this complex of proteins are cap-binding protein eIF4E and the eIF4E kinase Mnk1. Cap-dependent mRNA translation generally correlates with Mnk1 phosphorylation of eIF4E when both are bound to ..
  91. Das F, Ghosh Choudhury N, Bera A, Kasinath B, Choudhury G. TGF?-induced PI 3 kinase-dependent Mnk-1 activation is necessary for Ser-209 phosphorylation of eIF4E and mesangial cell hypertrophy. J Cell Physiol. 2013;228:1617-26 pubmed publisher
    ..Moreover, we conclude that TGF?-induced noncanonical signaling circuit involving PI 3 kinase-dependent Mnk-1-mediated phosphorylation of eIF4E at Ser-209 is required to facilitate mesangial cell hypertrophy. ..
  92. Shi Y, Frost P, Hoang B, Yang Y, Bardeleben C, Gera J, et al. MNK1-induced eIF-4E phosphorylation in myeloma cells: a pathway mediating IL-6-induced expansion and expression of genes involved in metabolic and proteotoxic responses. PLoS ONE. 2014;9:e94011 pubmed publisher
    ..IL-6 activated MNK1 phosphorylation and induced phosphorylation of its substrate, eIF-4E, in MM lines and primary specimens...