Gene Symbol: Map2k2
Description: mitogen-activated protein kinase kinase 2
Alias: AA589381, MEK2, MK2, Prkmk2, dual specificity mitogen-activated protein kinase kinase 2, ERK activator kinase 2, MAP kinase kinase 2, MAP kinase/Erk kinase, MAPK/ERK kinase 2, MAPKK 2, MEK 2, protein kinase, mitogen activated, kinase 2, p45
Species: mouse
Products:     Map2k2

Top Publications

  1. Fyhrquist N, Matikainen S, Lauerma A. MK2 signaling: lessons on tissue specificity in modulation of inflammation. J Invest Dermatol. 2010;130:342-4 pubmed publisher
    b>MK2 is a promising candidate for treating inflammation. Mice deficient in MK2 were studied in models of inflammation to see whether MK2 could be a useful target in inflammatory skin disease...
  2. Scholl F, Dumesic P, Barragan D, Harada K, Bissonauth V, Charron J, et al. Mek1/2 MAPK kinases are essential for Mammalian development, homeostasis, and Raf-induced hyperplasia. Dev Cell. 2007;12:615-29 pubmed a single level of this signaling pathway in mammals, and to investigate functional redundancy between Mek1 and Mek2, we disrupted these genes in murine and human epidermis...
  3. Ronkina N, Kotlyarov A, Dittrich Breiholz O, Kracht M, Hitti E, Milarski K, et al. The mitogen-activated protein kinase (MAPK)-activated protein kinases MK2 and MK3 cooperate in stimulation of tumor necrosis factor biosynthesis and stabilization of p38 MAPK. Mol Cell Biol. 2007;27:170-81 pubmed
    b>MK2 and MK3 represent protein kinases downstream of p38 mitogen-activated protein kinase (MAPK)...
  4. Kotlyarov A, Yannoni Y, Fritz S, Laass K, Telliez J, Pitman D, et al. Distinct cellular functions of MK2. Mol Cell Biol. 2002;22:4827-35 pubmed
    Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2) is activated upon stress by p38 MAPK alpha and -beta, which bind to a basic docking motif in the C terminus of MK2 and which subsequently phosphorylate its ..
  5. Bissonauth V, Roy S, Gravel M, Guillemette S, Charron J. Requirement for Map2k1 (Mek1) in extra-embryonic ectoderm during placentogenesis. Development. 2006;133:3429-40 pubmed
    ..Although the activation of MAP2K1 and MAP2K2 is widespread in the labyrinthine region, MAPK1 and MAPK3 activation is restricted to the cells lining the ..
  6. Bélanger L, Roy S, Tremblay M, Brott B, Steff A, Mourad W, et al. Mek2 is dispensable for mouse growth and development. Mol Cell Biol. 2003;23:4778-87 pubmed
    ..gene is present in Caenorhabditis elegans, Drosophila melanogaster, and Xenopus laevis, two Mek homologs, Mek1 and Mek2, are present in the mammalian cascade...
  7. Vertii A, Hakim C, Kotlyarov A, Gaestel M. Analysis of properties of small heat shock protein Hsp25 in MAPK-activated protein kinase 2 (MK2)-deficient cells: MK2-dependent insolubilization of Hsp25 oligomers correlates with susceptibility to stress. J Biol Chem. 2006;281:26966-75 pubmed
    ..of endogenous sHsp in a genetic model lacking the major Hsp25 kinase, the MAP kinase-activated protein kinase MK2. We demonstrate that in MK2-deficient fibroblasts, where no stress-dependent phosphorylation of Hsp25 at Ser86 and ..
  8. Nadeau V, Guillemette S, Bélanger L, Jacob O, Roy S, Charron J. Map2k1 and Map2k2 genes contribute to the normal development of syncytiotrophoblasts during placentation. Development. 2009;136:1363-74 pubmed publisher
    The mammalian genome contains two ERK/MAP kinase kinase genes, Map2k1 and Map2k2, which encode dual-specificity kinases responsible for ERK/MAP kinase activation...
  9. Zhong J, Li X, McNamee C, Chen A, Baccarini M, Snider W. Raf kinase signaling functions in sensory neuron differentiation and axon growth in vivo. Nat Neurosci. 2007;10:598-607 pubmed
    ..We conclude that Raf function is crucial for several aspects of DRG neuron development, including differentiation and axon growth. ..

More Information


  1. Scholl F, Dumesic P, Barragan D, Harada K, Charron J, Khavari P. Selective role for Mek1 but not Mek2 in the induction of epidermal neoplasia. Cancer Res. 2009;69:3772-8 pubmed publisher
    ..Mutations in this pathway have been associated with carcinogenesis and developmental disorders, making Mek1 and Mek2 prime therapeutic targets...
  2. Zheng C, Guan K. Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2. J Biol Chem. 1993;268:11435-9 pubmed
    ..MEK (MAP kinase or ERK kinase) is the immediate upstream activator kinase of ERK. Two cDNAs, MEK1 and MEK2, were cloned and sequenced. MEK1 and MEK2 encode 393 and 400 amino acid residues, respectively...
  3. Norrby M, Tagerud S. Mitogen-activated protein kinase-activated protein kinase 2 (MK2) in skeletal muscle atrophy and hypertrophy. J Cell Physiol. 2010;223:194-201 pubmed publisher
    ..The present study tests the hypothesis that MK2, a substrate of p38 which following phosphorylation, can be exported from the nucleus in a complex with p38, may be ..
  4. Huang Y, Li R, Chen X, Zhuo Y, Jin R, Qian X, et al. Doxycycline up-regulates the expression of IL-6 and GM-CSF via MAPK/ERK and NF-?B pathways in mouse thymic epithelial cells. Int Immunopharmacol. 2011;11:1143-9 pubmed publisher
    ..These findings warrant further investigation into the potential application of Dox in T-cell reconstitution in such situations as chemotherapy, radiotherapy, bone marrow transplantation and HIV infection. ..
  5. Damarla M, Parniani A, Johnston L, Maredia H, Serebreni L, Hamdan O, et al. Mitogen-activated protein kinase-activated protein kinase 2 mediates apoptosis during lung vascular permeability by regulating movement of cleaved caspase 3. Am J Respir Cell Mol Biol. 2014;50:932-41 pubmed publisher
    ..In contrast, MK2(-/-) mice are protected from pulmonary vascular permeability and apoptosis in response to LPS...
  6. Kunnen S, Leonhard W, Semeins C, Hawinkels L, Poelma C, Ten Dijke P, et al. Fluid shear stress-induced TGF-?/ALK5 signaling in renal epithelial cells is modulated by MEK1/2. Cell Mol Life Sci. 2017;74:2283-2298 pubmed publisher
    ..We conclude that fluid shear stress induces autocrine TGF-?/ALK5-induced target gene expression in renal epithelial cells, which is partially restrained by MEK1/2-mediated signaling. ..
  7. Yamashita S, Tai P, Charron J, Ko C, Ascoli M. The Leydig cell MEK/ERK pathway is critical for maintaining a functional population of adult Leydig cells and for fertility. Mol Endocrinol. 2011;25:1211-22 pubmed publisher
    MAPK kinase (MEK)1 and MEK2 were deleted from Leydig cells by crossing Mek1(f/f);Mek2(-/-) and Cyp17iCre mice...
  8. Willard M, Willard F, Li X, Cappell S, Snider W, Siderovski D. Selective role for RGS12 as a Ras/Raf/MEK scaffold in nerve growth factor-mediated differentiation. EMBO J. 2007;26:2029-40 pubmed
    ..that RGS12 associates with the nerve growth factor (NGF) receptor tyrosine kinase TrkA, activated H-Ras, B-Raf, and MEK2 and facilitates their coordinated signaling to prolonged ERK activation...
  9. Boucherat O, Landry Truchon K, Aoidi R, Houde N, Nadeau V, Charron J, et al. Lung development requires an active ERK/MAPK pathway in the lung mesenchyme. Dev Dyn. 2017;246:72-82 pubmed publisher
    ..Lung development necessitates a functional ERK/MAPK pathway in the lung mesenchymal layer in order to coordinate efficient epithelial-mesenchymal interactions. Developmental Dynamics 246:72-82, 2017. © 2016 Wiley Periodicals, Inc. ..
  10. Rastogi R, Jiang Z, Ahmad N, Rosati R, Liu Y, Beuret L, et al. Rapamycin induces mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) expression through activation of protein kinase B and mitogen-activated protein kinase kinase pathways. J Biol Chem. 2013;288:33966-77 pubmed publisher
    ..from wild-type (WT) mice or mice deficient in AKT1 and AKT2 isoforms or BMDM from targeted deficiency in MEK1 and MEK2, we show that rapamycin treatment led to an increased MKP1 expression in BMDM from WT but failed to do so in BMDMs ..
  11. Pan C, Liou Y, Low B. Active Mek2 as a regulatory scaffold that promotes Pin1 binding to BPGAP1 to suppress BPGAP1-induced acute Erk activation and cell migration. J Cell Sci. 2010;123:903-16 pubmed publisher
    ..BPGAP1 also interacted with wild-type and constitutively active Mek2, but not with its kinase-dead mutant...
  12. Kocieniewski P, Lipniacki T. MEK1 and MEK2 differentially control the duration and amplitude of the ERK cascade response. Phys Biol. 2013;10:035006 pubmed publisher
    ..In particular, MEK1 is subject to a negative feedback from activated ERK, which is further conferred to MEK2 via hetero-dimerization...
  13. Soukup K, Halfmann A, Le Bras M, Sahin E, Vittori S, Poyer F, et al. The MAPK-Activated Kinase MK2 Attenuates Dendritic Cell-Mediated Th1 Differentiation and Autoimmune Encephalomyelitis. J Immunol. 2015;195:541-52 pubmed publisher
    ..In this study we show an opposing role of MK2, by which it consolidates immune regulatory functions in DCs through modulation of p38, ERK1/2-MAPK, and STAT3 ..
  14. Noël A, Poitras I, Julien J, Petry F, Morin F, Charron J, et al. ERK (MAPK) does not phosphorylate tau under physiological conditions in vivo or in vitro. Neurobiol Aging. 2015;36:901-2 pubmed publisher
    ..Finally, ERK1/2 was inhibited, but tau phosphorylation was not altered in Mek1-/- mice. In conclusion, these results do not support the involvement of ERK1/2 in tau phosphorylation under physiological conditions. ..
  15. Catalanotti F, Reyes G, Jesenberger V, Galabova Kovacs G, de Matos Simoes R, Carugo O, et al. A Mek1-Mek2 heterodimer determines the strength and duration of the Erk signal. Nat Struct Mol Biol. 2009;16:294-303 pubmed publisher
    Mek1 and Mek2 (also known as Map2k1 and Map2k2, respectively) are evolutionarily conserved, dual-specificity kinases that mediate Erk1 and Erk2 activation during adhesion and growth factor signaling...
  16. Tsioumpekou M, Papadopoulos N, Burovic F, Heldin C, Lennartsson J. Platelet-derived growth factor (PDGF)-induced activation of Erk5 MAP-kinase is dependent on Mekk2, Mek1/2, PKC and PI3-kinase, and affects BMP signaling. Cell Signal. 2016;28:1422-31 pubmed publisher
    ..Thus, PDGF-BB-induced Erk5 activation involves parallel stimulatory and inhibitory pathways and promotes Smad1/5/8 signaling. ..
  17. Kamio N, Akifusa S, Yamaguchi N, Yamashita Y. Induction of granulocyte colony-stimulating factor by globular adiponectin via the MEK-ERK pathway. Mol Cell Endocrinol. 2008;292:20-5 pubmed publisher
    ..Collectively, these results suggest that MEK1/2-ERK1/2 signaling is involved in the adiponectin-induced secretion of G-CSF. ..
  18. Aoidi R, Maltais A, Charron J. Functional redundancy of the kinases MEK1 and MEK2: Rescue of the Mek1 mutant phenotype by Mek2 knock-in reveals a protein threshold effect. Sci Signal. 2016;9:ra9 pubmed publisher
    The mammalian genome contains two mitogen-activated protein kinase (MAPK) kinase (MEK)-encoding genes, Mek1 and Mek2. MEKs phosphorylate and activate the two extracellular signal-regulated kinase (ERK) isoforms ERK1 and ERK2...
  19. Schottelius A, Zugel U, Döcke W, Zollner T, Rose L, Mengel A, et al. The role of mitogen-activated protein kinase-activated protein kinase 2 in the p38/TNF-alpha pathway of systemic and cutaneous inflammation. J Invest Dermatol. 2010;130:481-91 pubmed publisher
    Mitogen-activated protein kinase-activated protein kinase 2 (MK2) is a downstream molecule of p38, involved in the production of TNF-alpha, a key cytokine, and an established drug target for many inflammatory diseases...
  20. Gorska M, Liang Q, Stafford S, Goplen N, Dharajiya N, Guo L, et al. MK2 controls the level of negative feedback in the NF-kappaB pathway and is essential for vascular permeability and airway inflammation. J Exp Med. 2007;204:1637-52 pubmed
    We demonstrate that mitogen-activated protein kinase-activated kinase-2 (MK2) is essential for localized Th2-type inflammation and development of experimental asthma...
  21. Choi T, Fukasawa K, Zhou R, Tessarollo L, Borror K, Resau J, et al. The Mos/mitogen-activated protein kinase (MAPK) pathway regulates the size and degradation of the first polar body in maturing mouse oocytes. Proc Natl Acad Sci U S A. 1996;93:7032-5 pubmed
    ..These studies identify meiotic spindle formation and programmed degradation of the first polar body as new and important roles for the Mos/MAPK pathway. ..
  22. Kotlyarov A, Gaestel M. Is MK2 (mitogen-activated protein kinase-activated protein kinase 2) the key for understanding post-transcriptional regulation of gene expression?. Biochem Soc Trans. 2002;30:959-63 pubmed
    The phenotype of mitogen-activated protein kinase-activated protein kinase-2 (MK2) knockout mice revealed the essential role of this enzyme in post-transcriptional regulation of lipopolysaccharide-induced expression of cytokines such as ..
  23. Tan A, Wong S, Lam K. Regulation of mouse inducible costimulator (ICOS) expression by Fyn-NFATc2 and ERK signaling in T cells. J Biol Chem. 2006;281:28666-78 pubmed
    ..Moreover, ectopic expression of NFATc2 or a constitutively active MEK2 amplifies ICOS transcription and transactivates a 288-bp core region of the icos promoter in luciferase reporter ..
  24. Bomar J, Benke P, Slattery E, Puttagunta R, Taylor L, Seong E, et al. Mutations in a novel gene encoding a CRAL-TRIO domain cause human Cayman ataxia and ataxia/dystonia in the jittery mouse. Nat Genet. 2003;35:264-9 pubmed
    ..Three-dimensional protein structural modeling predicts that the caytaxin ligand is more polar than vitamin E. Identification of the caytaxin ligand may help develop a therapy for Cayman ataxia. ..
  25. Zheng C, Lin Z, Zhao Z, Yang Y, Niu H, Shen X. MAPK-activated protein kinase-2 (MK2)-mediated formation and phosphorylation-regulated dissociation of the signal complex consisting of p38, MK2, Akt, and Hsp27. J Biol Chem. 2006;281:37215-26 pubmed
    ..protein 27 (hsp27) form a signaling complex with serine/threonine kinase Akt and MAPK-activated protein kinase-2 (MK2), which plays an important role in controlling stress-induced apoptosis and reorganizing actin cytoskeleton...
  26. Galabova Kovacs G, Matzen D, Piazzolla D, Meissl K, Plyushch T, Chen A, et al. Essential role of B-Raf in ERK activation during extraembryonic development. Proc Natl Acad Sci U S A. 2006;103:1325-30 pubmed
    ..The data demonstrate that B-Raf plays a nonredundant role in ERK activation during extraembyronic mammalian development in vivo. ..
  27. Vithayathil J, Pucilowska J, Goodnough L, ATIT R, Landreth G. Dentate Gyrus Development Requires ERK Activity to Maintain Progenitor Population and MAPK Pathway Feedback Regulation. J Neurosci. 2015;35:6836-48 pubmed publisher
    ..These findings establish that ERK signaling regulates maintenance of progenitor cells required for development of the dentate gyrus. ..
  28. Zhu J, Wu X, Goel S, Gowda N, Kumar S, Krishnegowda G, et al. MAPK-activated protein kinase 2 differentially regulates plasmodium falciparum glycosylphosphatidylinositol-induced production of tumor necrosis factor-{alpha} and interleukin-12 in macrophages. J Biol Chem. 2009;284:15750-61 pubmed publisher
    ..In this study, we investigated the role of MAPK-activated protein kinase 2 (MK2) in the regulation of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-12, two of the major ..
  29. Hislop N, Caddy J, Ting S, Auden A, Vasudevan S, King S, et al. Grhl3 and Lmo4 play coordinate roles in epidermal migration. Dev Biol. 2008;321:263-72 pubmed publisher
    ..Keratinocytes from mutant mice fail to "heal" in in vitro scratch assays, consistent with a general epidermal migratory defect that is dependent on ERK activation and actin cable formation...
  30. Tietz A, Malo A, Diebold J, Kotlyarov A, Herbst A, Kolligs F, et al. Gene deletion of MK2 inhibits TNF-alpha and IL-6 and protects against cerulein-induced pancreatitis. Am J Physiol Gastrointest Liver Physiol. 2006;290:G1298-306 pubmed
    ..The MAPKAPK-2 (MK2) signaling pathway is involved in cytokine gene expression...
  31. Cho K, Cai J, Kim H, Hosoya A, Ohshima H, Choi K, et al. ERK activation is involved in tooth development via FGF10 signaling. J Exp Zool B Mol Dev Evol. 2009;312:901-11 pubmed publisher
    ..The reported results will improve our understanding of the unique developmental processes of the dental epithelium and tooth growth, and will help to elucidate the fundamental mechanisms of ERK signaling underlying tooth development. ..
  32. Alessandrini A, Brott B, Erikson R. Differential expression of MEK1 and MEK2 during mouse development. Cell Growth Differ. 1997;8:505-11 pubmed
    Map/Erk kinase 1 (MEK1) and MEK2 activate the Erk/ MAP kinases and have been implicated in cell growth and differentiation...
  33. Kim K, Kim J, Wang Y, Sul H. Pref-1 (preadipocyte factor 1) activates the MEK/extracellular signal-regulated kinase pathway to inhibit adipocyte differentiation. Mol Cell Biol. 2007;27:2294-308 pubmed
    ..We conclude that Pref-1 activates MEK/ERK signaling, which is required for Pref-1 inhibition of adipogenesis. ..
  34. Pearson H, Perez Mancera P, Dow L, Ryan A, Tennstedt P, Bogani D, et al. SCRIB expression is deregulated in human prostate cancer, and its deficiency in mice promotes prostate neoplasia. J Clin Invest. 2011;121:4257-67 pubmed publisher
    ..These data suggest that the polarity network could provide a new avenue for therapeutic intervention. ..
  35. Nadeau V, Bissonauth V, Charron J. [Mek1 and Mek2 functions in the formation of the blood placental barrier]. Med Sci (Paris). 2012;28:409-15 pubmed publisher
    ..MEK1 and MEK2 are double specificity serine-threonine/tyrosine kinases responsible for the activation of ERK1 and ERK2...
  36. Li X, Newbern J, Wu Y, Morgan Smith M, Zhong J, Charron J, et al. MEK Is a Key Regulator of Gliogenesis in the Developing Brain. Neuron. 2012;75:1035-50 pubmed publisher
    ..Radial progenitors deficient in both Mek1 and Mek2 fail to transition to the gliogenic mode in late embryogenesis, and astrocyte and oligodendroglial precursors fail ..
  37. Pages G, Stanley E, Le Gall M, Brunet A, Pouyssegur J. The mouse p44 mitogen-activated protein kinase (extracellular signal-regulated kinase 1) gene. Genomic organization and structure of the 5'-flanking regulatory region. J Biol Chem. 1995;270:26986-92 pubmed
    ..This result implicates a major role of this region that contains the Sp1 sites.(ABSTRACT TRUNCATED AT 400 WORDS) ..
  38. Choi J, Huebner A, Clement K, Walsh R, Savol A, Lin K, et al. Prolonged Mek1/2 suppression impairs the developmental potential of embryonic stem cells. Nature. 2017;548:219-223 pubmed publisher
  39. Crews C, Erikson R. Purification of a murine protein-tyrosine/threonine kinase that phosphorylates and activates the Erk-1 gene product: relationship to the fission yeast byr1 gene product. Proc Natl Acad Sci U S A. 1992;89:8205-9 pubmed
    ..These data are discussed with regard to a possible signal transduction mechanism. ..
  40. Cazaubon S, Ramos Morales F, Fischer S, Schweighoffer F, Strosberg A, Couraud P. Endothelin induces tyrosine phosphorylation and GRB2 association of Shc in astrocytes. J Biol Chem. 1994;269:24805-9 pubmed
    ..In conclusion, the Shc-Grb2 complex may be involved in the activation of the MAPK pathway, not only by several receptor tyrosine kinases but also by heterotrimeric G protein-coupled receptors, such as ET-1 receptors. ..
  41. Yeoh G, Ernst M, Rose John S, Akhurst B, Payne C, Long S, et al. Opposing roles of gp130-mediated STAT-3 and ERK-1/ 2 signaling in liver progenitor cell migration and proliferation. Hepatology. 2007;45:486-94 pubmed
    ..Hyperactive STAT-3 signaling results in enhanced oval cell numbers, whereas ERK-1/2 activation suppresses oval cell proliferation. ..
  42. Blasco R, Francoz S, Santamaria D, Canamero M, Dubus P, Charron J, et al. c-Raf, but not B-Raf, is essential for development of K-Ras oncogene-driven non-small cell lung carcinoma. Cancer Cell. 2011;19:652-63 pubmed publisher
    ..These results indicate that c-Raf plays a unique role in mediating K-Ras signaling and makes it a suitable target for therapeutic intervention. ..
  43. Hu J, Chen T, Zhuang Z, Kong L, Yu M, Liu Y, et al. Feedback control of MKP-1 expression by p38. Cell Signal. 2007;19:393-400 pubmed
    ..Depletion of MAPKAP kinase 2 (MK2), a downstream substrate of p38, by RNAi also inhibited the expression of MKP-1...
  44. Xiong B, Yu L, Wang Q, Ai J, Yin S, Liu J, et al. Regulation of intracellular MEK1/2 translocation in mouse oocytes: cytoplasmic dynein/dynactin-mediated poleward transport and cyclin B degradation-dependent release from spindle poles. Cell Cycle. 2007;6:1521-7 pubmed
  45. Elsaid A, Délot E, Collins M. Differential perturbation of the Fgf/Erk1/2 and Shh pathways in the C57BL/6N and SWV embryonic limb buds after mid-gestational cadmium chloride administration. Mol Genet Metab. 2007;92:258-70 pubmed
    ..The data of the present study indicate that a differential strain response to CdCl(2)-induced forelimb digital loss may be due to a polymorphic interference with the Fgf/Shh positive feedback loop and Erk1/2 phosphorylation. ..
  46. Goettel J, Liang D, Hilliard V, Edelblum K, Broadus M, Gould K, et al. KSR1 is a functional protein kinase capable of serine autophosphorylation and direct phosphorylation of MEK1. Exp Cell Res. 2011;317:452-63 pubmed publisher
    ..These data provide clear evidence that KSR1 is a functional protein kinase, MEK1 is an in vitro substrate of KSR1, and the catalytic activities of both proteins are required for eliciting cell survival responses downstream of TNF. ..
  47. Huang Z, Chen J, Regan J, Maguire C, Tang R, Dong X, et al. Loss of microRNAs in neural crest leads to cardiovascular syndromes resembling human congenital heart defects. Arterioscler Thromb Vasc Biol. 2010;30:2575-86 pubmed publisher
    ..Our results uncovered a central role for Dicer and miRNAs in NCC survival, migration, and patterning in craniofacial and cardiovascular development which, when mutated, lead to congenital neuro-craniofacial-cardiac defects. ..
  48. Brott B, Alessandrini A, Largaespada D, Copeland N, Jenkins N, Crews C, et al. MEK2 is a kinase related to MEK1 and is differentially expressed in murine tissues. Cell Growth Differ. 1993;4:921-9 pubmed
    ..We report the cloning of a second MEK-like complementary DNA, Mek2, which predicts a protein of a molecular weight of 44,500...
  49. Newbern J, Zhong J, Wickramasinghe R, Li X, Wu Y, Samuels I, et al. Mouse and human phenotypes indicate a critical conserved role for ERK2 signaling in neural crest development. Proc Natl Acad Sci U S A. 2008;105:17115-20 pubmed publisher
    ..Inactivation of upstream elements of the ERK cascade (B-Raf and C-Raf, MEK1 and MEK2) or a downstream effector, the transcription factor serum response factor resulted in analogous developmental ..
  50. Eales K, Palygin O, O Loughlin T, Rasooli Nejad S, Gaestel M, M Ller J, et al. The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility. Nat Commun. 2014;5:4701 pubmed publisher
    ..Here we provide evidence that MAPK-activated protein kinases 2 and 3 (MK2/3) regulate neuronal spine morphology, synaptic transmission and plasticity...
  51. Hitti E, Iakovleva T, Brook M, Deppenmeier S, Gruber A, Radzioch D, et al. Mitogen-activated protein kinase-activated protein kinase 2 regulates tumor necrosis factor mRNA stability and translation mainly by altering tristetraprolin expression, stability, and binding to adenine/uridine-rich element. Mol Cell Biol. 2006;26:2399-407 pubmed
    The mitogen-activated protein kinase (MAPK) p38/MAPK-activated protein kinase 2 (MK2) signaling pathway plays an important role in the posttranscriptional regulation of tumor necrosis factor (TNF), which is dependent on the adenine/..
  52. Wang Y, Wang F, Sun T, Trostinskaia A, Wygle D, Puscheck E, et al. Entire mitogen activated protein kinase (MAPK) pathway is present in preimplantation mouse embryos. Dev Dyn. 2004;231:72-87 pubmed
    ..2003] Development 130:4527-4537). This spatial and temporal expression study lays a foundation to plan and analyze perturbation studies aimed at understanding the role of the major mitogenic pathway in preimplantation mouse embryos. ..
  53. 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
    ..MNK1 may define a convergence point between the growth factor-activated and one of the stress-activated protein kinase cascades and is a candidate to phosphorylate eIF-4E in cells. ..
  54. Morandell S, Reinhardt H, Cannell I, Kim J, Ruf D, Mitra T, et al. A reversible gene-targeting strategy identifies synthetic lethal interactions between MK2 and p53 in the DNA damage response in vivo. Cell Rep. 2013;5:868-77 pubmed publisher
    ..The stress-activated p38 mitogen-activated protein kinase (MAPK)/MAPKAP kinase-2 (MK2) pathway is a critical component of the DDR network in p53-deficient tumor cells in vitro...
  55. Conche C, Boulla G, Trautmann A, Randriamampita C. T cell adhesion primes antigen receptor-induced calcium responses through a transient rise in adenosine 3',5'-cyclic monophosphate. Immunity. 2009;30:33-43 pubmed publisher
    ..Thus, whereas sustained cAMP increases are well known to inhibit TCR signaling, transient cAMP increases occurring physiologically upon formation of an immunological synapse facilitate antigen detection. ..
  56. Taguchi K, Matsumoto T, Kamata K, Kobayashi T. Angiotensin II type 2 receptor-dependent increase in nitric oxide synthase activity in the endothelium of db/db mice is mediated via a MEK pathway. Pharmacol Res. 2012;66:41-50 pubmed publisher
    ..Lean) mice. The preservation of such AT(2)R function during AT(1)R blockade needs to be considered in the search for a physiological role for AT(2)R. ..
  57. Nordström E, Luhr K, Ibanez C, Kristensson K. Inhibitors of the mitogen-activated protein kinase kinase 1/2 signaling pathway clear prion-infected cells from PrPSc. J Neurosci. 2005;25:8451-6 pubmed
    ..We conclude that inhibitors of the MEK1/2 pathway can efficiently and probably irreversibly clear PrP(Sc) from prion-infected cells. The MEK pathway may therefore be a suitable target for therapeutic intervention in prion diseases. ..
  58. Plath K, Engel K, Schwedersky G, Gaestel M. Characterization of the proline-rich region of mouse MAPKAP kinase 2: influence on catalytic properties and binding to the c-abl SH3 domain in vitro. Biochem Biophys Res Commun. 1994;203:1188-94 pubmed
    ..The data suggest that the proline-rich region of MAPKAP kinase 2 could interact with proteins containing SH3-domains also in vivo regulating its cellular localization and/or modulating its enzymatic properties. ..
  59. Zaru R, Edgar A, Hanauer A, Watts C. Structural and functional basis for p38-MK2-activated Rsk signaling in toll-like receptor-stimulated dendritic cells. Mol Cell Biol. 2015;35:132-40 pubmed publisher
    ..cells (DC) Rsk is also activated by p38 mitogen-activated protein (MAP) kinase via its downstream substrates, MK2/3...
  60. Remeseiro S, Cuadrado A, Kawauchi S, Calof A, Lander A, Losada A. Reduction of Nipbl impairs cohesin loading locally and affects transcription but not cohesion-dependent functions in a mouse model of Cornelia de Lange Syndrome. Biochim Biophys Acta. 2013;1832:2097-102 pubmed publisher
    ..These results provide further support for the idea that developmental defects in CdLS are caused by deregulated transcription and not by malfunction of cohesion-related processes. ..
  61. Krenz M, Gulick J, Osinska H, Colbert M, Molkentin J, Robbins J. Role of ERK1/2 signaling in congenital valve malformations in Noonan syndrome. Proc Natl Acad Sci U S A. 2008;105:18930-5 pubmed publisher
    ..The data demonstrate both necessity and sufficiency of increased ERK activation downstream of Shp2 in mediating abnormal valve development in a NS mouse model...
  62. Dungan C, Williamson D. Regulation of skeletal muscle insulin-stimulated signaling through the MEK-REDD1-mTOR axis. Biochem Biophys Res Commun. 2017;482:1067-1072 pubmed publisher
    ..These data support that REDD1 is required for normal insulin-stimulated signaling, and that a subtle balance exists between MEK1/2, REDD1, and mTOR for the proper regulation of insulin signaling. ..
  63. Gerhardt C, Lier J, Kuschel S, Ruther U. The ciliary protein Ftm is required for ventricular wall and septal development. PLoS ONE. 2013;8:e57545 pubmed publisher
    ..Thus, our study suggests ciliopathy as a cause of VSDs. ..
  64. 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
    ..abrogating the pathway activity in mice lacking simultaneously dual-specificity protein kinases Mek1 and Mek2. Our data show that MAPK pathway is heterogeneously activated in the subset of G1- and S-phase epithelial cells, ..
  65. O Donovan K, Ma K, Guo H, Wang C, Sun F, Han S, et al. B-RAF kinase drives developmental axon growth and promotes axon regeneration in the injured mature CNS. J Exp Med. 2014;211:801-14 pubmed publisher
    ..We conclude that cell-intrinsic RAF signaling is a crucial pathway promoting developmental and regenerative axon growth in the peripheral and central nervous systems. ..
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