Mapkapk2

Summary

Gene Symbol: Mapkapk2
Description: MAP kinase-activated protein kinase 2
Alias: AA960234, MAPKAP-K2, MK-2, MK2, Rps6kc1, MAP kinase-activated protein kinase 2, MAPK-activated protein kinase 2, MAPKAP kinase 2
Species: mouse

Top Publications

  1. pmc MAPKAP kinase MK2 maintains self-renewal capacity of haematopoietic stem cells
    Jessica Schwermann
    Institute of Biochemistry, Hannover Medical School, Hannover, Germany
    EMBO J 28:1392-406. 2009
  2. pmc Mitogen activated protein kinase activated protein kinase 2 regulates actin polymerization and vascular leak in ventilator associated lung injury
    Mahendra Damarla
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
    PLoS ONE 4:e4600. 2009
  3. ncbi MAPKAP kinase 2-deficient mice are resistant to collagen-induced arthritis
    Martin Hegen
    Inflammation Department, Wyeth Research, Cambridge, MA 02140, USA
    J Immunol 177:1913-7. 2006
  4. pmc 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
    N Ronkina
    Institute of Biochemistry, Medical School Hannover, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    Mol Cell Biol 27:170-81. 2007
  5. pmc 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
    Edward Hitti
    Medical School Hannover, Institute of Biochemistry, Carl Neuberg Str 1, D 30625 Hannover, Germany
    Mol Cell Biol 26:2399-407. 2006
  6. pmc MK2 controls the level of negative feedback in the NF-kappaB pathway and is essential for vascular permeability and airway inflammation
    Magdalena M Gorska
    Division of Allergy and Immunology, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA
    J Exp Med 204:1637-52. 2007
  7. ncbi MK2-/- gene knockout mouse hearts carry anti-apoptotic signal and are resistant to ischemia reperfusion injury
    Keisuke Shiroto
    Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT 06030 1110, USA
    J Mol Cell Cardiol 38:93-7. 2005
  8. ncbi Systemic deficiency of the MAP kinase-activated protein kinase 2 reduces atherosclerosis in hypercholesterolemic mice
    Kumaravelu Jagavelu
    Department of Cardiology and Angiology, Hannover Medical School, Carl Neuberg Str 01, 30625 Hannover, Germany
    Circ Res 101:1104-12. 2007
  9. doi MAPKAP kinase 2-deficiency prevents neurons from cell death by reducing neuroinflammation--relevance in a mouse model of Parkinson's disease
    Tobias Thomas
    Institute of Biochemistry, Hannover Medical School, Hannover, Germany
    J Neurochem 105:2039-52. 2008
  10. ncbi MAPKAP kinase 2 phosphorylates tristetraprolin on in vivo sites including Ser178, a site required for 14-3-3 binding
    Carol A Chrestensen
    Department of Pharmacology, University of Virginia Health Sciences Center, Charlottesville 22908, USA
    J Biol Chem 279:10176-84. 2004

Scientific Experts

  • Lale Ozcan
  • Anje Cauwels
  • Simon Rousseau
  • Xinkang Wang
  • M Hegen
  • Ainsley A Culbert
  • Shuang Huang
  • Martin D Lehner
  • Xiaowei Gong
  • Matthias Gaestel
  • Alexey Kotlyarov
  • Manoj B Menon
  • Tobias Thomas
  • Danuta Radzioch
  • Thusanth Thuraisingam
  • Natalia Ronkina
  • Tiegang Liu
  • Christian Ehlting
  • Edward Hitti
  • Adam J Guess
  • A Kotlyarov
  • Ruma Pengal
  • Udo Bavendiek
  • Bernhard Schieffer
  • M Gaestel
  • Chi Kuang Huang
  • Yue Wu
  • Usamah S Kayyali
  • Kumaravelu Jagavelu
  • Jessica Schwermann
  • Johannes G Bode
  • Claus Schafer
  • Antje Malo
  • Burkhard Goke
  • Claus Johansen
  • J Simon C Arthur
  • Najoua Lalaoui
  • Anita L Ray
  • Bethany A Herbert
  • Anne Limbourg
  • Klara Soukup
  • Benjamin Vandendriessche
  • Silvia M Tietz
  • Katharina Köther
  • Piyushkumar R Kapopara
  • Stefanie Schumacher
  • Keisuke Shiroto
  • Thomas Michler
  • Martin Storr
  • Sungguan Hong
  • Xiaodong Liu
  • Madeleine Scharf
  • Karl Katholnig
  • Yu Y Li
  • Kyung Sun Heo
  • Joshua Manley
  • Shih Pei Lin
  • William E Smoyer
  • Darui Xu
  • Joanna Jagielska
  • Rainer Benndorf
  • Shipra Agrawal
  • Christopher Tiedje
  • George Kollias
  • Achim D Gruber
  • Mirita Franz-Wachtel
  • Yibin Yang
  • Nicholas S Hill
  • Talin Ebrahimian
  • Kirsty F MacKenzie
  • Stephanie Ochs
  • Rod R Warburton
  • Shuai Lv
  • Stephan Ludwig
  • Francesco P Marchese
  • Simone Radtke
  • Arndt J Schottelius
  • Ian G Cannell
  • Ju Yuan
  • Nader Ghasemlou
  • Yu Shi
  • Petra Gais
  • John M Streicher
  • Lars Iversen
  • Anne T Funding
  • Yong Yu Li
  • Knud Kragballe
  • Jianzhong Zhu
  • Diana A Gorog
  • Alyssa Bouska

Detail Information

Publications83

  1. pmc MAPKAP kinase MK2 maintains self-renewal capacity of haematopoietic stem cells
    Jessica Schwermann
    Institute of Biochemistry, Hannover Medical School, Hannover, Germany
    EMBO J 28:1392-406. 2009
    The structurally related MAPK-activated protein kinases (MAPKAPKs or MKs) MK2, MK3 and MK5 are involved in multiple cellular functions, including cell-cycle control and cellular differentiation...
  2. pmc Mitogen activated protein kinase activated protein kinase 2 regulates actin polymerization and vascular leak in ventilator associated lung injury
    Mahendra Damarla
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
    PLoS ONE 4:e4600. 2009
    ..We postulated that MK2 activation via p38 MAP kinase induced HSP25 phosphorylation, in response to mechanical stress, leading to actin ..
  3. ncbi MAPKAP kinase 2-deficient mice are resistant to collagen-induced arthritis
    Martin Hegen
    Inflammation Department, Wyeth Research, Cambridge, MA 02140, USA
    J Immunol 177:1913-7. 2006
    ..b>MAPKAP kinase 2 (MK2) is a serine/threonine kinase that is regulated through direct phosphorylation by p38 MAPK, and has been ..
  4. pmc 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
    N Ronkina
    Institute of Biochemistry, Medical School Hannover, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    Mol Cell Biol 27:170-81. 2007
    b>MK2 and MK3 represent protein kinases downstream of p38 mitogen-activated protein kinase (MAPK)...
  5. pmc 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
    Edward Hitti
    Medical School Hannover, Institute of Biochemistry, Carl Neuberg Str 1, D 30625 Hannover, Germany
    Mol Cell Biol 26:2399-407. 2006
    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/..
  6. pmc MK2 controls the level of negative feedback in the NF-kappaB pathway and is essential for vascular permeability and airway inflammation
    Magdalena M Gorska
    Division of Allergy and Immunology, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA
    J Exp Med 204:1637-52. 2007
    We demonstrate that mitogen-activated protein kinase-activated kinase-2 (MK2) is essential for localized Th2-type inflammation and development of experimental asthma...
  7. ncbi MK2-/- gene knockout mouse hearts carry anti-apoptotic signal and are resistant to ischemia reperfusion injury
    Keisuke Shiroto
    Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT 06030 1110, USA
    J Mol Cell Cardiol 38:93-7. 2005
    ..potentiates activation of p38 MAP kinase (p38MAPK) leading to the activation of its downstream target MAPKAP kinase 2 (MK2)...
  8. ncbi Systemic deficiency of the MAP kinase-activated protein kinase 2 reduces atherosclerosis in hypercholesterolemic mice
    Kumaravelu Jagavelu
    Department of Cardiology and Angiology, Hannover Medical School, Carl Neuberg Str 01, 30625 Hannover, Germany
    Circ Res 101:1104-12. 2007
    ..regulator of inflammatory processes represents the mitogen-activated protein kinase-activated protein kinase-2 (MK2)...
  9. doi MAPKAP kinase 2-deficiency prevents neurons from cell death by reducing neuroinflammation--relevance in a mouse model of Parkinson's disease
    Tobias Thomas
    Institute of Biochemistry, Hannover Medical School, Hannover, Germany
    J Neurochem 105:2039-52. 2008
    ..A role for the p38 stress-activated protein kinase/MAPK-activated protein kinase 2 (MK2) axis in inflammation and apoptosis is well documented...
  10. ncbi MAPKAP kinase 2 phosphorylates tristetraprolin on in vivo sites including Ser178, a site required for 14-3-3 binding
    Carol A Chrestensen
    Department of Pharmacology, University of Virginia Health Sciences Center, Charlottesville 22908, USA
    J Biol Chem 279:10176-84. 2004
    b>MAPKAP kinase 2 (MK2) is required for tumor necrosis factor synthesis. Tristetraprolin (TTP) binds to the 3'-untranslated region of tumor necrosis factor mRNA and regulates its fate...
  11. pmc Inhibition of the protein kinase MK-2 protects podocytes from nephrotic syndrome-related injury
    Ruma Pengal
    Center for Clinical and Translational Research, The Research Institute at Nationwide Children s Hospital, Columbus, OH 43205, USA
    Am J Physiol Renal Physiol 301:F509-19. 2011
    ....
  12. pmc Distinct functions of the mitogen-activated protein kinase-activated protein (MAPKAP) kinases MK2 and MK3: MK2 mediates lipopolysaccharide-induced signal transducers and activators of transcription 3 (STAT3) activation by preventing negative regulatory ef
    Christian Ehlting
    Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich Heine University, D 40225 Dusseldorf, Germany
    J Biol Chem 286:24113-24. 2011
    ..kinase (MK) 2 and MK3 for LPS-induced STAT3 activation in macrophages, the present study provides evidence that MK2 is crucial for STAT3 activation in response to LPS because it prevents MK3 from impeding IFNβ gene expression...
  13. ncbi Mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 deficiency protects brain from ischemic injury in mice
    Xinkang Wang
    Department of Cardiovascular Sciences, Bristol Myers Squibb Company, Wilmington, Delaware 19880 0400, USA
    J Biol Chem 277:43968-72. 2002
    Mitogen-activated protein (MAP) kinase-activated protein kinase 2 (MK2) is one of several kinases directly regulated by p38 MAP kinase...
  14. pmc Distinct cellular functions of MK2
    Alexey Kotlyarov
    Institute of Biochemistry, Medical School Hannover, Hannover 30625, Germany
    Mol Cell Biol 22:4827-35. 2002
    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 ..
  15. ncbi Mitogen-activated protein kinase-activated protein kinase 2-deficient mice show increased susceptibility to Listeria monocytogenes infection
    Martin D Lehner
    Department of Biochemical Pharmacology, University of Konstanz, Konstanz, Germany
    J Immunol 168:4667-73. 2002
    Mitogen-activated protein kinase-activated protein kinase 2 (MK2) is one of several kinases activated through direct phosphorylation by p38 mitogen-activated protein kinase...
  16. ncbi MK2 targets AU-rich elements and regulates biosynthesis of tumor necrosis factor and interleukin-6 independently at different post-transcriptional levels
    Armin Neininger
    Innovationskolleg Zellspezialisierung, Martin Luther Universitat Halle Wittenberg, 06120 Halle, Germany
    J Biol Chem 277:3065-8. 2002
    We demonstrate that lipopolysaccharide-induced tumor necrosis factor (TNF) biosynthesis becomes independent of MAPKAP kinase 2 (MK2) when the AU-rich element (ARE) of the TNF gene is deleted...
  17. doi Mitogen-activated protein kinase-activated protein kinase 2 (MK2) contributes to secondary damage after spinal cord injury
    Nader Ghasemlou
    Centre for Research in Neuroscience, The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
    J Neurosci 30:13750-9. 2010
    ..In this work, we identified mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MAPKAPK2 or MK2), a downstream substrate of p38 MAPK, as a potential target using microarray analysis of contused spinal ..
  18. ncbi MAPKAP kinase 2 is essential for LPS-induced TNF-alpha biosynthesis
    A Kotlyarov
    Martin Luther University Halle Wittenberg, Germany
    Nat Cell Biol 1:94-7. 1999
    b>MAPKAP kinase 2 (MK2) is one of several kinases that are regulated through direct phosphorylation by p38 MAP kinase. By introducing a targeted mutation into the mouse MK2 gene, we have determined the physiological function of MK2 in vivo...
  19. pmc Leptomycin B-sensitive nuclear export of MAPKAP kinase 2 is regulated by phosphorylation
    K Engel
    Max Delbruck Center for Molecular Medicine, Berlin, Germany
    EMBO J 17:3363-71. 1998
    To study the intracellular localization of MAPKAP kinase 2 (MK2), which carries a putative bipartite nuclear localization signal (NLS), we constructed a green fluorescent protein-MAPKAP kinase 2 fusion protein (GFP-MK2)...
  20. pmc p38 MAP kinase and MAPKAP kinases MK2/3 cooperatively phosphorylate epithelial keratins
    Manoj B Menon
    Institute of Biochemistry, Medical School Hannover, Hannover 30625, Germany
    J Biol Chem 285:33242-51. 2010
    The MAPK-activated protein kinases (MAPKAP kinases) MK2 and MK3 are directly activated via p38 MAPK phosphorylation, stabilize p38 by complex formation, and contribute to the stress response...
  21. pmc Interleukin-10 targets p38 MAPK to modulate ARE-dependent TNF mRNA translation and limit intestinal pathology
    D Kontoyiannis
    Institute of Immunology, BSRC Alexander Fleming, 166 72 Vari, Greece
    EMBO J 20:3760-70. 2001
    ..This cross-talk is necessary for optimal TNF production and for the maintenance of immune homeostasis in the gut...
  22. doi Targeting p38 or MK2 Enhances the Anti-Leukemic Activity of Smac-Mimetics
    Najoua Lalaoui
    Cell Signaling and Cell Death and Cancer and Hematology Divisions, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia Department of Medical Biology, University of Melbourne, Parkville, VIC 3050, Australia
    Cancer Cell 29:145-58. 2016
    ..even though p38 is required for Toll-like receptors to induce TNF, loss of p38 or its downstream kinase MK2 increased induction of TNF by SM...
  23. pmc Signaling by p38 MAPK stimulates nuclear localization of the microprocessor component p68 for processing of selected primary microRNAs
    Sungguan Hong
    Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Health Sciences University, Augusta, GA 30912, USA
    Sci Signal 6:ra16. 2013
    ..the mitogen-activated protein kinase (MAPK) p38 and its downstream effector kinase MAPK-activated protein kinase 2 (MK2) were necessary for the efficient processing of a subset of primary miRNAs (pri-miRNAs)...
  24. pmc Mitogen-activated protein kinase-activated protein kinases 2 and 3 regulate SERCA2a expression and fiber type composition to modulate skeletal muscle and cardiomyocyte function
    Madeleine Scharf
    Department of Biochemistry, Hannover Medical School, Hannover, Germany
    Mol Cell Biol 33:2586-602. 2013
    The mitogen-activated protein kinase (MAPK)-activated protein kinases 2 and 3 (MK2/3) represent protein kinases downstream of the p38 MAPK...
  25. doi Inhibition of MK2 shows promise for preventing postoperative ileus in mice
    Xiaodong Liu
    Department of Colon and Rectal Surgery, Union Clinical Medical College, Fujjian Medical University, Fuzhou, China
    J Surg Res 185:102-12. 2013
    ..Mitogen-activated protein kinase-activated protein kinase 2 (MK2) plays an essential role in inflammation and is an established drug target for many inflammatory diseases...
  26. doi MAPKAP kinase 3 suppresses Ifng gene expression and attenuates NK cell cytotoxicity and Th1 CD4 T-cell development upon influenza A virus infection
    Katharina Köther
    Institute of Molecular Virology IMV, Centre for Molecular Biology of Inflammation ZMBE, and
    FASEB J 28:4235-46. 2014
    b>MK2 and MK3 are downstream targets of p38 and ERK1/2. They control the mRNA stability of several inflammatory cytokines, including TNF-α and IL-10...
  27. pmc MK2 and Fas receptor contribute to the severity of CNS demyelination
    Silvia M Tietz
    Department of Neurology, Justus Liebig University Giessen, Giessen, Germany Theodor Kocher Institute, Universtiy of Bern, Bern, Switzerland
    PLoS ONE 9:e100363. 2014
    Models of inflammatory or degenerative diseases demonstrated that the protein-kinase MK2 is a key player in inflammation...
  28. pmc MAPK-activated protein kinase 2-deficiency causes hyperacute tumor necrosis factor-induced inflammatory shock
    Benjamin Vandendriessche
    Inflammation Research Center, VIB, Ghent, 9052, Belgium
    BMC Physiol 14:5. 2014
    MAPK-activated protein kinase 2 (MK2) plays a pivotal role in the cell response to (inflammatory) stress...
  29. pmc MAP-Kinase Activated Protein Kinase 2 Links Endothelial Activation and Monocyte/macrophage Recruitment in Arteriogenesis
    Anne Limbourg
    Vascular Medicine Research, Dept of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany Integriertes Forschungs und Behandlungszentrum Transplantation IFB Tx, Hannover Medical School, Hannover, Germany
    PLoS ONE 10:e0138542. 2015
    ..However, little is known how these processes are coordinated. The MAP-kinase-activated-proteinkinase-2 (MK2) is a critical regulator of inflammatory processes and might represent an important link between cytokine ..
  30. pmc Sexual Dimorphism in MAPK-Activated Protein Kinase-2 (MK2) Regulation of RANKL-Induced Osteoclastogenesis in Osteoclast Progenitor Subpopulations
    Bethany A Herbert
    Department of Oral Health Sciences and the Center for Oral Health Research, Medical University of South Carolina, Charleston, South Carolina, United States of America
    PLoS ONE 10:e0125387. 2015
    ..However the role of the p38 MAPK substrate, MAPK-activated protein kinase 2 (MK2), is not clearly delineated...
  31. pmc Blockade of MK2 is protective in inflammation-associated colorectal cancer development
    Anita L Ray
    Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM
    Int J Cancer 138:770-5. 2016
    Chronic inflammation is a risk factor for colorectal cancer. The MAPK-activated protein kinase 2 (MK2) pathway controls multiple cellular processes including p38-dependent inflammation...
  32. pmc Anthrax lethal toxin-induced lung injury and treatment by activating MK2
    Tiegang Liu
    Pulmonary, Critical Care, and Sleep Division, Department of Medicine Tupper Research Institute, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts
    J Appl Physiol (1985) 119:412-9. 2015
    ..were linked specifically to blocking activation of p38 substrate and MAP kinase-activated protein kinase 2 (MAPKAPK2 or MK2) and phosphorylation of the latter's substrate, heat shock protein 27 (HSP27)...
  33. doi The MAPK-Activated Kinase MK2 Attenuates Dendritic Cell-Mediated Th1 Differentiation and Autoimmune Encephalomyelitis
    Klara Soukup
    Department of Immunology, St Anna Children s Cancer Research Institute, 1090 Vienna, Austria
    J Immunol 195:541-52. 2015
    ..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 ..
  34. pmc Treatment of Obese Insulin-Resistant Mice With an Allosteric MAPKAPK2/3 Inhibitor Lowers Blood Glucose and Improves Insulin Sensitivity
    Lale Ozcan
    Department of Medicine, Columbia University, New York, NY
    Diabetes 64:3396-405. 2015
    ..calcium/calmodulin-dependent protein kinase II (CaMKII), p38α mitogen-activated protein kinase (MAPK), and MAPKAPK2/3 (MK2/3). Genetic-based inhibition of these kinases improves metabolism in obese mice...
  35. doi Endoplasmic reticulum-associated ubiquitin-conjugating enzyme Ube2j1 is a novel substrate of MK2 (MAPKAP kinase-2) involved in MK2-mediated TNFα production
    Manoj B Menon
    Institute of Physiological Chemistry, Hannover Medical School, Carl Neuberg Str 1, D 30625 Hannover, Germany
    Biochem J 456:163-72. 2013
    The p38 MAPK (mitogen-activated protein kinase)/MK2 [MAPKAP (MAPK-activated protein) kinase-2] signalling pathway is a major regulator of stress- and cytokine-induced gene expression at the transcriptional and post-transcriptional level...
  36. pmc Sequence and structural analyses of nuclear export signals in the NESdb database
    Darui Xu
    Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
    Mol Biol Cell 23:3677-93. 2012
    ..Finally, we also tested CRM1-binding of 40 NESs that were found in the 56 structures. We found that 16 of the NES peptides did not bind CRM1, hence illustrating how NESs are easily misidentified...
  37. pmc Inhibition of SAPK2a/p38 prevents hnRNP A0 phosphorylation by MAPKAP-K2 and its interaction with cytokine mRNAs
    Simon Rousseau
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, MSI WTB complex, Dow Street, Dundee DD1 5EH, UK E mail
    EMBO J 21:6505-14. 2002
    ..Our data suggest that LPS-induced binding of hnRNP A0 to AREs may contribute to the post-transcriptional regulation of specific mRNAs...
  38. doi Interleukin-1 assembles a proangiogenic signaling module consisting of caveolin-1, tumor necrosis factor receptor-associated factor 6, p38-mitogen-activated protein kinase (MAPK), and MAPK-activated protein kinase 2 in endothelial cells
    Joanna Jagielska
    Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
    Arterioscler Thromb Vasc Biol 32:1280-8. 2012
    ..However, signaling pathways mediating IL-1β-induced proangiogenic processes in endothelial cells (ECs) have barely been elucidated yet. Therefore, the present study investigated IL-1β-induced proangiogenic signaling in ECs...
  39. doi Activation of cannabinoid receptor 2 reduces inflammation in acute experimental pancreatitis via intra-acinar activation of p38 and MK2-dependent mechanisms
    Thomas Michler
    Department of Medicine II, Ludwig Maximilians University, Munich, Germany
    Am J Physiol Gastrointest Liver Physiol 304:G181-92. 2013
    ..Cerulein pancreatitis was induced in wild-type, CB(1)-/-, and MK2-/- mice pretreated with selective cannabinoid receptor agonists or antagonists...
  40. pmc Survival of cancer stem cells under hypoxia and serum depletion via decrease in PP2A activity and activation of p38-MAPKAPK2-Hsp27
    Shih Pei Lin
    Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan
    PLoS ONE 7:e49605. 2012
    ..Hsp27 activation, which was mediated by the p38MAPK-MAPKAPK2-Hsp27 pathway, is required for CD133+ cells to inhibit caspase 9 and 3 cleavage...
  41. pmc Phosphorylation of protein inhibitor of activated STAT1 (PIAS1) by MAPK-activated protein kinase-2 inhibits endothelial inflammation via increasing both PIAS1 transrepression and SUMO E3 ligase activity
    Kyung Sun Heo
    Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    Arterioscler Thromb Vasc Biol 33:321-9. 2013
    ..The aim of the study is to elucidate the regulatory mechanisms for these 2 different functions, especially with respect to endothelial inflammation...
  42. pmc p38α senses environmental stress to control innate immune responses via mechanistic target of rapamycin
    Karl Katholnig
    Clinical Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria
    J Immunol 190:1519-27. 2013
    ..Our data link p38α to mTOR signaling in myeloid immune cells that is decisive for tuning the immune response in dependence on the environmental milieu...
  43. pmc Crucial roles of the protein kinases MK2 and MK3 in a mouse model of glomerulonephritis
    Adam J Guess
    Center for Clinical and Translational Research, The Research Institute at Nationwide Children s Hospital, Columbus, Ohio, United States of America
    PLoS ONE 8:e54239. 2013
    ..p38 MAPK signaling is partially mediated through MK2 and MK3, two phylogenetically related protein kinases that are its direct substrates...
  44. doi Inhibition of p38/Mk2 signaling pathway improves the anti-inflammatory effect of WIN55 on mouse experimental colitis
    Yu Y Li
    Department of Pathophysiology, Institute of Digestive Disease, Tongji University School of Medicine, Shanghai, China
    Lab Invest 93:322-33. 2013
    P38/Mk2 (mitogen-activated protein kinase (MAPK)-activated protein kinase-2, also known as MAKAP kinase-2) is a member of the mitogen-activated protein kinases (MAPKs) family, and participates in inflammatory responses directly or ..
  45. pmc A cytosolic ATM/NEMO/RIP1 complex recruits TAK1 to mediate the NF-kappaB and p38 mitogen-activated protein kinase (MAPK)/MAPK-activated protein 2 responses to DNA damage
    Yibin Yang
    Departments of Cancer Biology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA
    Mol Cell Biol 31:2774-86. 2011
    ..These findings have translational implications and reveal RIP1 and TAK1 as potential therapeutic targets in chemoresistance...
  46. doi Phosphorylation of cAMP-specific PDE4A5 (phosphodiesterase-4A5) by MK2 (MAPKAPK2) attenuates its activation through protein kinase A phosphorylation
    Kirsty F MacKenzie
    Molecular Pharmacology Group, Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, Wolfson Link and Davidson Buildings, University of Glasgow, Glasgow G12 8QQ, Scotland, U K
    Biochem J 435:755-69. 2011
    ..region 1) domain conserved among PDE4 long isoforms, by MK2 (MAPK-activated protein kinase 2, also called MAPKAPK2)...
  47. pmc Mitogen-activated protein kinase-activated protein kinase 2 in angiotensin II-induced inflammation and hypertension: regulation of oxidative stress
    Talin Ebrahimian
    Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, Montreal, Quebec, Canada
    Hypertension 57:245-54. 2011
    ..We questioned whether mitogen-activated protein kinase-activated protein kinase 2 (MK2), a downstream target of p38 mitogen-activated protein kinase, is involved in angiotensin II-induced vascular ..
  48. pmc MAPK-activated protein kinase 2 differentially regulates plasmodium falciparum glycosylphosphatidylinositol-induced production of tumor necrosis factor-{alpha} and interleukin-12 in macrophages
    Jianzhong Zhu
    Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 284:15750-61. 2009
    ..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 ..
  49. pmc MAPK-activated protein kinase 2 is required for mouse meiotic spindle assembly and kinetochore-microtubule attachment
    Ju Yuan
    State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    PLoS ONE 5:e11247. 2010
    MAPK-activated protein kinase 2 (MK2), a direct substrate of p38 MAPK, plays key roles in multiple physiological functions in mitosis. Here, we show for the first time the unique distribution pattern of MK2 in meiosis...
  50. pmc MAPKAP kinase 2 blocks tristetraprolin-directed mRNA decay by inhibiting CAF1 deadenylase recruitment
    Francesco P Marchese
    Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, London W6 8LH, United Kingdom
    J Biol Chem 285:27590-600. 2010
    ..The p38 MAPK pathway regulates mRNA stability via the downstream kinase MAPK-activated protein kinase 2 (MAPKAP kinase 2 or MK2), which phosphorylates and prevents the mRNA-destabilizing function of TTP...
  51. doi Mechanisms regulating the nuclear translocation of p38 MAP kinase
    Xiaowei Gong
    Department of Pathophysiology, Key Laboratory of Proteomics of Gongdong Province, Southern Medical University, Guangzhou 510515, China
    J Cell Biochem 110:1420-9. 2010
    ..On the other hand, the nuclear export of p38 requires its dephosphorylation, and it is exported both in a MK2-dependent and a nuclear export signal (NES)-independent manner...
  52. ncbi ERK1/2-activated de novo Mapkapk2 synthesis is essential for osteogenic growth peptide mitogenic signaling in osteoblastic cells
    Symone M San Miguel
    Bone Laboratory, The Hebrew University of Jerusalem, Israel
    J Biol Chem 280:37495-502. 2005
    ..is critically dependent on de novo synthesis of mitogen-activated protein kinase-activated protein kinase 2 (Mapkapk2) mRNA and protein...
  53. ncbi Distinct role of MAPKAPK-2 in the regulation of TNF gene expression by Toll-like receptor 7 and 9 ligands
    Thusanth Thuraisingam
    McGill University, Department of Human Genetics, Montreal General Hospital Research Institute, Montreal, Que, Canada
    Mol Immunol 44:3482-91. 2007
    ..Here we report that activation of the p38 MAPK/MK2 pathway is crucial for both S28463- and CpG-induced cytokine and chemokine production...
  54. ncbi MAPKAPK2-mediated LSP1 phosphorylation and FMLP-induced neutrophil polarization
    Yue Wu
    Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA
    Biochem Biophys Res Commun 358:170-5. 2007
    In neutrophils, the major substrate of MAPKAPK2 (MK2) is an F-actin binding protein LSP1...
  55. ncbi Ischemic preconditioning involves dual cardio-protective axes with p38MAPK as upstream target
    Norbert Nagy
    FAHA Cardiovascular Research Center, University of Connecticut School of Medicine Farmington, Cardiovascular Research Institute, CT 06030 1110, USA
    J Mol Cell Cardiol 42:981-90. 2007
    ..indicates a crucial role of p38 MAP (mitogen-activated protein) kinase (p38MAPK) and its downstream target MAPKAP kinase 2 (MK2) in ischemic preconditioning (IPC)...
  56. ncbi Regulation of suppressor of cytokine signaling 3 (SOCS3) mRNA stability by TNF-alpha involves activation of the MKK6/p38MAPK/MK2 cascade
    Christian Ehlting
    Department of Gastroenterology, Hepatology and Infectiology, Heinrich Heine University, Moorenstrasse 5, Dusseldorf, Germany
    J Immunol 178:2813-26. 2007
    ..In fibroblasts or macrophages deficient for MAPK-activated protein kinase 2 (MK2), a downstream target of the MKK6/p38(MAPK) cascade, basal SOCS3-expression is strongly reduced and TNF-alpha-..
  57. pmc Combinatorial pattern recognition receptor signaling alters the balance of life and death in macrophages
    Tracie A Seimon
    Department of Medicine and Anatomy, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 103:19794-9. 2006
    ..PRR-induced macrophage death may play important roles in advanced atherosclerosis and in other innate immunity-related processes in which the balance between macrophage survival and death is critical...
  58. pmc M line-deficient titin causes cardiac lethality through impaired maturation of the sarcomere
    Stefanie Weinert
    Neuromuscular and Cardiovascular Cell Biology, Max Delbruck Center for Molecular Medicine, D 13125 Berlin Buch, Germany
    J Cell Biol 173:559-70. 2006
    ....
  59. ncbi Gene deletion of MK2 inhibits TNF-alpha and IL-6 and protects against cerulein-induced pancreatitis
    Anne Barbara Tietz
    Department of Internal Medicine II, Klinikum Grosshadern, Munich, Germany
    Am J Physiol Gastrointest Liver Physiol 290:G1298-306. 2006
    ..The MAPKAPK-2 (MK2) signaling pathway is involved in cytokine gene expression...
  60. pmc Ablation of MEKK4 kinase activity causes neurulation and skeletal patterning defects in the mouse embryo
    Amy N Abell
    Department of Pharmacology, University of North Carolina, Chapel Hill, 27599 7365, USA
    Mol Cell Biol 25:8948-59. 2005
    ..Together, these data demonstrate MEKK4 regulation of p38 and that substrates downstream of p38 control cellular homeostasis. The findings are the first demonstration that MEKK4-regulated p38 activity is critical for neurulation...
  61. pmc Lack of MK2 inhibits myofibroblast formation and exacerbates pulmonary fibrosis
    Tiegang Liu
    Pulmonary and Critical Care Division, Department of Medicine Tupper Research Institute, Tufts New England Medical Center, and Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    Am J Respir Cell Mol Biol 37:507-17. 2007
    ..We have recently described a role for MK2 in this phenotypic differentiation in culture...
  62. ncbi HDM2 phosphorylation by MAPKAP kinase 2
    Hans Oliver Weber
    The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK
    Oncogene 24:1965-72. 2005
    ..Here, we show that MAPKAP kinase 2 (MK2) can phosphorylate HDM2 on serine 157 and 166 in vitro...
  63. pmc Scaffolding by ERK3 regulates MK5 in development
    Stefanie Schumacher
    Medical School Hannover, Institute of Biochemistry, Hannover, Germany
    EMBO J 23:4770-9. 2004
    ..Deletion of MK5 leads to strong reduction of ERK3 protein levels and embryonic lethality at about stage E11, where ERK3 expression in wild-type mice is maximum, indicating a role of this signalling module in development...
  64. ncbi A requirement of MAPKAPK2 in the uropod localization of PTEN during FMLP-induced neutrophil chemotaxis
    Yue Wu
    Department of Pathology, University of Connecticut, Farmington, CT, USA
    Biochem Biophys Res Commun 316:666-72. 2004
    ..b>MK2(-/-) neutrophils have a directionality loss in fMLP-induced chemotaxis...
  65. pmc Elimination of protein kinase MK5/PRAK activity by targeted homologous recombination
    Yu Shi
    Institute of Biochemistry, Medical School Hannover, 30625 Hannover, Germany
    Mol Cell Biol 23:7732-41. 2003
    ..resulted in a phenotype very different from the complex inflammation-impaired phenotype of mice deficient in MK2, although MK2 and MK5 exhibit evolutional, structural, and apparent extensive functional similarities...
  66. pmc Genetic dissection of the cellular pathways and signaling mechanisms in modeled tumor necrosis factor-induced Crohn's-like inflammatory bowel disease
    Dimitris Kontoyiannis
    Institute for Immunology, Biomedical Sciences Research Center Al Fleming, Vari 166 72, Greece Division of Gastroenterology and Hepatology, University of Virginia Health Sciences Center, Charlottesville, VA 22906, USA
    J Exp Med 196:1563-74. 2002
    ..Interestingly, TNF-mediated intestinal pathology was exacerbated in the absence of MAPKAP kinase 2, yet strongly attenuated in a Cot/Tpl2 or JNK2 kinase-deficient genetic background...
  67. ncbi Abnormal migration phenotype of mitogen-activated protein kinase-activated protein kinase 2-/- neutrophils in Zigmond chambers containing formyl-methionyl-leucyl-phenylalanine gradients
    M O Hannigan
    Department of Pathology, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06030, USA
    J Immunol 167:3953-61. 2001
    ..were used to study the migration of wild-type (WT) and mitogen-activated protein kinase-activated protein kinase 2 (MK2-/-) mouse neutrophils in Zigmond chambers containing fMLP gradients...
  68. ncbi The MAP kinase-activated protein kinase 2 contains a proline-rich SH3-binding domain
    K Engel
    Max Delbrück Center of Molecular Medicine, Berlin, Germany
    FEBS Lett 336:143-7. 1993
    The protein sequence of MAP kinase-activated protein kinase 2 (MAPKAP kinase 2) deduced from mouse cDNA sequence reveals structural features of the enzyme, which could be of importance for its function: a proline-rich SH3-binding domain ..
  69. ncbi Regulation of HSP60 and the role of MK2 in a new model of severe experimental pancreatitis
    Yong Yu Li
    Department of Pathophysiology, School of Medicine, Tongji University, Shanghai, China
    Am J Physiol Gastrointest Liver Physiol 297:G981-9. 2009
    The objective of this study was to investigate the role of MAPKAP kinase 2 (MK2) and heat shock protein (HSP) HSP60 in the pathogenesis of a new model of severe acute pancreatitis (AP)...
  70. ncbi The MAPK-activated kinase Rsk controls an acute Toll-like receptor signaling response in dendritic cells and is activated through two distinct pathways
    Rossana Zaru
    Division of Cell Biology and Immunology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Nat Immunol 8:1227-35. 2007
    ..in DCs a previously unknown configuration of the MAPK system whereby Rsk is activated not only by Erk but also by p38 through the intermediates MK2 and MK3. Thus, in DCs, p38 contributes to the activation of all known MK families.
  71. doi MAP-kinase-activated protein kinase 2 expression and activity is induced after neuronal depolarization
    Tobias Thomas
    Institute of Biochemistry, Hannover Medical School, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    Eur J Neurosci 28:642-54. 2008
    ..Here, we describe a possible new function of MK2. We show that triggering depolarization by potassium chloride or increasing the cellular cAMP by forskolin ..
  72. doi Reduced oxazolone-induced skin inflammation in MAPKAP kinase 2 knockout mice
    Anne T Funding
    Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark
    J Invest Dermatol 129:891-8. 2009
    Mitogen-activated protein kinase (MAPK) AP kinase 2 (MK2) is a serine/threonine kinase that is phosphorylated and activated by p38 MAPK...
  73. pmc MAPKAPK-2 modulates p38-MAPK localization and small heat shock protein phosphorylation but does not mediate the injury associated with p38-MAPK activation during myocardial ischemia
    Diana A Gorog
    Cardiovascular Division, Department of Cardiology, King s College London School of Medicine, The Rayne Institute, St Thomas s Hospital, London SE1 7EH, UK
    Cell Stress Chaperones 14:477-89. 2009
    MAPKAPK-2 (MK2) is a protein kinase activated downstream of p38-MAPK which phosphorylates the small heat shock proteins HSP27 and alphaB crystallin and modulates p38-MAPK cellular distribution...
  74. pmc RIG-I-mediated activation of p38 MAPK is essential for viral induction of interferon and activation of dendritic cells: dependence on TRAF2 and TAK1
    Susie S Mikkelsen
    Institute of Medical Microbiology and Immunology, The Bartholin Building, University of Aarhus, DK 8000 Aarhus C, Denmark
    J Biol Chem 284:10774-82. 2009
    ..p38 MAPK exerted its function independent of the MAPK-activated protein kinases MK2, MNK, and MSK1/2. We also observed that TRAF2 and TAK1 were essential for RIG-I-mediated activation of p38 MAPK...
  75. doi Mdm2 affects genome stability independent of p53
    Alyssa Bouska
    Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, USA
    Cancer Res 69:1697-701. 2009
    ..In light of these findings, targeting Mdm2 in human malignancies may have effects other than activating p53...
  76. ncbi 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
    K Plath
    Max Delbrück Centrum for Molecular Medicine, Berlin, Germany
    Biochem Biophys Res Commun 203:1188-94. 1994
    ..to bind SH3 domains, we analyzed the interaction of the SH3 domain of the protein tyrosine kinase c-abl with MAPKAP kinase 2. It is demonstrated, that the proline-rich region specifically binds c-abl-SH3 domain in vitro...
  77. doi MAPKAPK-2 signaling is critical for cutaneous wound healing
    Thusanth Thuraisingam
    Department of Human Genetics, Montreal General Hospital Research Institute, McGill University, Montreal, Quebec, Canada
    J Invest Dermatol 130:278-86. 2010
    ..Mitogen-activated protein kinase (MAPK)-activated protein kinase-2 (MAPKAPK-2 or MK2), a major substrate of p38 MAPK, has been shown to be a major player in multiple inflammatory diseases, but its ..
  78. doi The role of mitogen-activated protein kinase-activated protein kinase 2 in the p38/TNF-alpha pathway of systemic and cutaneous inflammation
    Arndt J Schottelius
    Bayer Schering Pharma AG, Berlin, Germany
    J Invest Dermatol 130:481-91. 2010
    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...
  79. doi MK2 regulates the early stages of skin tumor promotion
    Claus Johansen
    Department of Dermatology, Aarhus University Hospital, P P Oerumsgade 11, 8000 Aarhus, Denmark
    Carcinogenesis 30:2100-8. 2009
    ..Mitogen-activated protein kinase-activated protein kinase-2 (MK2) is known to play a pivotal role in inflammatory processes...
  80. doi Cross-regulation of cytokine signalling: pro-inflammatory cytokines restrict IL-6 signalling through receptor internalisation and degradation
    Simone Radtke
    Department of Biochemistry and Molecular Biology, Medical School RWTH Aachen, 52074 Aachen, Germany
    J Cell Sci 123:947-59. 2010
    ..We identify MK2 as the kinase that phosphorylates serine 782 in the cytoplasmic part of gp130...
  81. pmc p38 MAPK/MK2-mediated induction of miR-34c following DNA damage prevents Myc-dependent DNA replication
    Ian G Cannell
    Center for Biomolecular Sciences, School of Pharmacy, University of Nottingham, University Park, Nottingham, NG7 2RD, UK
    Proc Natl Acad Sci U S A 107:5375-80. 2010
    ..and ATM (Ataxia telangiectasia mutated)/CHK2 pathways in addition to a newly identified ATM/ATR/p38MAPK/MK2 checkpoint...
  82. pmc MAPK-activated protein kinase-2 in cardiac hypertrophy and cyclooxygenase-2 regulation in heart
    John M Streicher
    Department of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles, CA 91301, USA
    Circ Res 106:1434-43. 2010
    ..The p38 kinase pathway also has a controversial role in cardiac hypertrophy. MAPK-activated protein kinase-2 (MK2) is a well-established p38 downstream kinase, yet its contribution to p38-mediated pathological response in heart ..
  83. doi TRIF signaling stimulates translation of TNF-alpha mRNA via prolonged activation of MK2
    Petra Gais
    Department of Surgery, Technical University of Munich, Munich, Germany
    J Immunol 184:5842-8. 2010
    ..The p38 effector kinase MK2 was directly activated through the TRIF pathway of TLR4...