Matthias Gaestel

Summary

Affiliation: Hannover Medical School
Country: Germany

Publications

  1. ncbi request reprint Characterization of the atypical MAPK ERK4 and its activation of the MAPK-activated protein kinase MK5
    Shashi Kant
    Institute of Biochemistry, Medical School Hannover, Hannover 30625, Germany
    J Biol Chem 281:35511-9. 2006
  2. ncbi request reprint Specificity of signaling from MAPKs to MAPKAPKs: kinases' tango nuevo
    Matthias Gaestel
    Department of Biochemistry, Hannover Medical School, Carl Neuberg Str 1, D30625 Hannover, Germany
    Front Biosci 13:6050-9. 2008
  3. doi request reprint NAMPT is essential for the G-CSF-induced myeloid differentiation via a NAD(+)-sirtuin-1-dependent pathway
    Julia Skokowa
    Department of Molecular Hematopoiesis, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Nat Med 15:151-8. 2009
  4. pmc Stress induced gene expression: a direct role for MAPKAP kinases in transcriptional activation of immediate early genes
    N Ronkina
    Institute of Biochemistry, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Nucleic Acids Res 39:2503-18. 2011
  5. ncbi request reprint MAPKAP kinases - MKs - two's company, three's a crowd
    Matthias Gaestel
    Department of Biochemistry, Medical School Hannover, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Nat Rev Mol Cell Biol 7:120-30. 2006
  6. ncbi request reprint Peptides as signaling inhibitors for mammalian MAP kinase cascades
    Matthias Gaestel
    Department of Biochemistry, Hannover Medical School, Carl Neuberg Str 1, 30625 Hannover, Germany
    Curr Pharm Des 15:2471-80. 2009
  7. ncbi request reprint Protein kinases as small molecule inhibitor targets in inflammation
    M Gaestel
    Department of Biochemistry, Hannover Medical School, Carl Neuberg Str 1, 30625 Hannover, Germany
    Curr Med Chem 14:2214-34. 2007
  8. doi request reprint Targeting innate immunity protein kinase signalling in inflammation
    Matthias Gaestel
    Hannover Medical School, Institute of Biochemistry, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Nat Rev Drug Discov 8:480-99. 2009
  9. doi request reprint Biological monitoring of non-thermal effects of mobile phone radiation: recent approaches and challenges
    Matthias Gaestel
    Institute of Biochemistry, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Biol Rev Camb Philos Soc 85:489-500. 2010
  10. ncbi request reprint 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
    Anastassiia Vertii
    Institute of Biochemistry, Medical School Hannover, Hannover 30625, Germany
    J Biol Chem 281:26966-75. 2006

Collaborators

Detail Information

Publications67

  1. ncbi request reprint Characterization of the atypical MAPK ERK4 and its activation of the MAPK-activated protein kinase MK5
    Shashi Kant
    Institute of Biochemistry, Medical School Hannover, Hannover 30625, Germany
    J Biol Chem 281:35511-9. 2006
    ..Interestingly, ERK4 dimerizes and/or oligomerizes with ERK3, suggesting that overexpressed inactive ERK3 recruits active endogenous ERK4 to MK5 for its activation. Hence, ERK3 and ERK4 cooperate in activation of MK5...
  2. ncbi request reprint Specificity of signaling from MAPKs to MAPKAPKs: kinases' tango nuevo
    Matthias Gaestel
    Department of Biochemistry, Hannover Medical School, Carl Neuberg Str 1, D30625 Hannover, Germany
    Front Biosci 13:6050-9. 2008
    ..These mechanisms enable specific MAPK pathways to act independently via specific MAPKAPKs but also allow different MAPK pathways to cooperate in downstream signalling in a coordinated fashion...
  3. doi request reprint NAMPT is essential for the G-CSF-induced myeloid differentiation via a NAD(+)-sirtuin-1-dependent pathway
    Julia Skokowa
    Department of Molecular Hematopoiesis, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Nat Med 15:151-8. 2009
    ..G-CSF, in turn, further increases NAMPT levels. These results reveal a decisive role of the NAD(+) metabolic pathway in G-CSF-triggered myelopoiesis...
  4. pmc Stress induced gene expression: a direct role for MAPKAP kinases in transcriptional activation of immediate early genes
    N Ronkina
    Institute of Biochemistry, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Nucleic Acids Res 39:2503-18. 2011
    ..Hence, a new function of MKs in transcriptional activation of IEGs via the p38α-MK2/3-SRF-axis is proposed which probably cooperates with MKs' role in posttranscriptional gene expression in inflammation and stress response...
  5. ncbi request reprint MAPKAP kinases - MKs - two's company, three's a crowd
    Matthias Gaestel
    Department of Biochemistry, Medical School Hannover, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Nat Rev Mol Cell Biol 7:120-30. 2006
    ....
  6. ncbi request reprint Peptides as signaling inhibitors for mammalian MAP kinase cascades
    Matthias Gaestel
    Department of Biochemistry, Hannover Medical School, Carl Neuberg Str 1, 30625 Hannover, Germany
    Curr Pharm Des 15:2471-80. 2009
    ..In addition to specifically targeting protein-protein interactions, the ultimate efficacy of these peptide inhibitors in vivo also depends on their delivery, stability and toxicity in living cells and in the whole organism...
  7. ncbi request reprint Protein kinases as small molecule inhibitor targets in inflammation
    M Gaestel
    Department of Biochemistry, Hannover Medical School, Carl Neuberg Str 1, 30625 Hannover, Germany
    Curr Med Chem 14:2214-34. 2007
    ..This overview should help to keep up with the fast developing field and the continuously growing number of protein kinase inhibitors...
  8. doi request reprint Targeting innate immunity protein kinase signalling in inflammation
    Matthias Gaestel
    Hannover Medical School, Institute of Biochemistry, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Nat Rev Drug Discov 8:480-99. 2009
    ....
  9. doi request reprint Biological monitoring of non-thermal effects of mobile phone radiation: recent approaches and challenges
    Matthias Gaestel
    Institute of Biochemistry, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Biol Rev Camb Philos Soc 85:489-500. 2010
    ..If successful, this strategy should contribute to identification of new underlying molecular mechanisms of interaction between RF-EMFs and living beings distinct from absorption of thermal energy...
  10. ncbi request reprint 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
    Anastassiia Vertii
    Institute of Biochemistry, Medical School Hannover, Hannover 30625, Germany
    J Biol Chem 281:26966-75. 2006
    ....
  11. pmc The extracellular signal-regulated kinase 3 (mitogen-activated protein kinase 6 [MAPK6])-MAPK-activated protein kinase 5 signaling complex regulates septin function and dendrite morphology
    Frank Brand
    Institute of Physiological Chemistry, Hannover Medical School, Hannover, Germany
    Mol Cell Biol 32:2467-78. 2012
    ..Thus, the regulation of neuronal morphogenesis is proposed as the first physiological function of the ERK3/MK5 signaling module...
  12. 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
    ..These data suggest that MK2 inhibits the mRNA destabilizing activity of TTP and, in parallel, codegradation of TTP together, with the target mRNA resulting in increased cellular levels of TTP...
  13. 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
    ..Therefore, MK2 and p38 MAPK function in concert to phosphorylate K8, K18, and K20 in intestinal epithelia...
  14. doi request reprint Monitoring protein-protein interactions in mammalian cells by trans-SUMOylation
    Ratnesh K Srivastav
    Institute for Physiological Chemistry Biochemistry, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Biochem J 438:495-503. 2011
    ..The ability of TRS to monitor protein interactions in mammalian cells in vivo at levels similar to endogenous expression makes it an excellent new tool that can help in defining the protein interactome of mammalian cells...
  15. doi request reprint 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
    ..Together, our data suggest a possible role of MK2 in the cellular response after neuronal depolarization, in particular in excitotoxicity...
  16. doi request reprint MAPKAP kinases MK2 and MK3 in inflammation: complex regulation of TNF biosynthesis via expression and phosphorylation of tristetraprolin
    Natalia Ronkina
    Institute of Biochemistry, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Biochem Pharmacol 80:1915-20. 2010
    ..A model is proposed, which demonstrates how this new function of transcriptional activation of TTP by MK2/3 cooperates with the role of MK2/3 in post-transcriptional gene expression to limit the inflammatory response...
  17. doi request reprint 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
    ..Interestingly, Ube2j1 is phosphorylated in response to LPS also in macrophages and contributes to MK2-dependent TNFα biosynthesis by a so far unknown mechanism...
  18. 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
    ..We conclude that the differences between the phenotypes of MK5- and MK2-deficient mice result from clearly different functional properties of both enzymes...
  19. 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...
  20. pmc The p38/MK2-driven exchange between tristetraprolin and HuR regulates AU-rich element-dependent translation
    Christopher Tiedje
    Institute of Biochemistry, Hannover Medical School, Hannover, Germany
    PLoS Genet 8:e1002977. 2012
    ..The phosphorylation-regulated TTP/HuR exchange at target mRNAs provides a reversible switch between unstable/non-translatable and stable/efficiently translated mRNAs...
  21. 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
    ..Thus, MK2 emerges as a regulator of HSC homeostasis, which could act through chromatin remodelling by the PcG complex...
  22. doi request reprint 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
    ....
  23. ncbi request reprint 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
    ..Therefore, MK2 might represent an attractive novel target for the treatment of atherosclerotic cardiovascular disease...
  24. doi request reprint Fluorescence-based quantitative scratch wound healing assay demonstrating the role of MAPKAPK-2/3 in fibroblast migration
    Manoj B Menon
    Institute of Biochemistry, Hannover Medical School, Carl Neuberg Strasse 1, Hannover, Germany
    Cell Motil Cytoskeleton 66:1041-7. 2009
    ..In addition, migration of MK2/3-double-deficient cells is determined and the ability of MK3 to rescue cell migration in MK2/3-double-deficient fibroblasts is demonstrated...
  25. pmc Ubc9 fusion-directed SUMOylation identifies constitutive and inducible SUMOylation
    Astrid Jakobs
    Institut fur Physiologische Chemie, Medizinische Hochschule Hannover, Carl Neuberg Street, 1, 30625 Hannover, Germany
    Nucleic Acids Res 35:e109. 2007
    ..Hence, UFDS is appropriate for the identification and characterization of constitutive and, more importantly, induced protein SUMOylation in vivo...
  26. 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
    ..Hence, the p38-MK2/3 axis may represent a novel target for the design of therapeutic strategies for diseases related to fiber type changes or impaired SERCA2 function...
  27. pmc Distinct cellular functions of MK2
    Alexey Kotlyarov
    Institute of Biochemistry, Medical School Hannover, Hannover 30625, Germany
    Mol Cell Biol 22:4827-35. 2002
    ..These data indicate that catalytic activity of MK2 is required for both cytokine production and cell migration. However, the proline-rich MK2 N terminus provides a distinct role restricted to cell migration...
  28. doi request reprint Deletion of MK2 signalling in vivo inhibits small Hsp phosphorylation but not diabetic nephropathy
    Joon Keun Park
    Department of Nephrology, Hannover Medical School, Hannover, Germany
    Nephrol Dial Transplant 23:1844-53. 2008
    ..Although activation of p38MAPK has been previously shown in diabetes mellitus, our results indicate that blockade of the downstream MK2/Hsp25 signalling pathway does not interfere with the development of early diabetic nephropathy...
  29. ncbi request reprint MK2 and MK3--a pair of isoenzymes?
    Natalia Ronkina
    Department of Biochemistry, Hannover Medical School, Carl Neuberg Str 1, D30625 Hannover, Germany
    Front Biosci 13:5511-21. 2008
    ..MK2-knockout mice show decreased LPS-induced cytokine biosynthesis and increased protection against collagen-induced arthritis. Recently generated MK2/3 double knockout mice show further reduction of LPS-induced cytokine production...
  30. pmc SB202190-induced cell type-specific vacuole formation and defective autophagy do not depend on p38 MAP kinase inhibition
    Manoj B Menon
    Institute of Biochemistry, Hannover Medical School, Hannover, Germany
    PLoS ONE 6:e23054. 2011
    ....
  31. doi request reprint Signal integration, crosstalk mechanisms and networks in the function of inflammatory cytokines
    M Lienhard Schmitz
    Institute of Biochemistry, Justus Liebig University Giessen, Giessen, Germany
    Biochim Biophys Acta 1813:2165-75. 2011
    ....
  32. ncbi request reprint In the cellular garden of forking paths: how p38 MAPKs signal for downstream assistance
    Yu Shi
    Hannover Medical School, Institute of Biochemistry, Carl Neuberg Str 1, D 30625 Hannover, Germany
    Biol Chem 383:1519-36. 2002
    ..For that reason, we will focus in this review on the different signalling events that are triggered by p38 activity, and analyse how these events contribute to specific gene expression and cellular responses...
  33. doi request reprint Small-molecule protein and lipid kinase inhibitors in inflammation and specific models for their evaluation
    Matthias Gaestel
    Hannover Medical School, Institute of Biochemistry, Hannover, Germany
    Methods Mol Biol 795:35-44. 2012
    ..Finally, it is discussed how the results obtained by these methods can be further validated and which future strategies for the treatment of chronic inflammation will exist...
  34. pmc Mutually exclusive STAT1 modifications identified by Ubc9/substrate dimerization-dependent SUMOylation
    Susan Zimnik
    Institute for Physiological Chemistry Biochemistry, Medical School Hannover, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Nucleic Acids Res 37:e30. 2009
    ....
  35. doi request reprint Molecular mechanisms of phosphorylation-regulated TTP (tristetraprolin) action and screening for further TTP-interacting proteins
    Christopher Tiedje
    Institute of Biochemistry, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Biochem Soc Trans 38:1632-7. 2010
    ....
  36. ncbi request reprint Affinity purification of ARE-binding proteins identifies polyA-binding protein 1 as a potential substrate in MK2-induced mRNA stabilization
    Frank Bollig
    Institute of Pharmacology, Medical School Hannover, Germany
    Biochem Biophys Res Commun 301:665-70. 2003
    ..The selective interaction with an ARE-containing RNA and the phosphorylation by MK2 suggest that PABP1 plays a regulatory role in ARE-dependent mRNA decay and its modulation by the p38 MAP kinase cascade...
  37. ncbi request reprint Ubc9 fusion-directed SUMOylation (UFDS): a method to analyze function of protein SUMOylation
    Astrid Jakobs
    Institut fur Physiologische Chemie, Medizinische Hochschule Hannover, Carl Neuberg Str 1, 30625 Hannover, Germany
    Nat Methods 4:245-50. 2007
    ..We propose that UFDS will be useful for the analysis of function of SUMOylation in protein interactions, subcellular localization as well as enzymatic activity...
  38. 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
    ..This finding, together with the observation that ectopically expressed MK3 can rescue MK2 deficiency similarly to MK2, indicates that both kinases share the same physiological function in vivo but are expressed to different levels...
  39. ncbi request reprint Is MK2 (mitogen-activated protein kinase-activated protein kinase 2) the key for understanding post-transcriptional regulation of gene expression?
    A Kotlyarov
    Medical School Hannover, Institute of Biochemistry, Carl Neuberg Strasse 1, Germany
    Biochem Soc Trans 30:959-63. 2002
    ..Here we discuss the possible mechanisms by which two potential target proteins of MK2, small heat-shock protein 25/27 (Hsp25/27) and tristetraprolin, could contribute to our understanding of the above regulation...
  40. ncbi request reprint Identification of a phosphorylation site on skeletal muscle myosin light chain kinase that becomes phosphorylated during muscle contraction
    Claire E Haydon
    MRC Protein Phosphorylation Unit, University of Dundee, Dundee, DD1 5EH, Scotland, UK
    Arch Biochem Biophys 397:224-31. 2002
    ..The sequence surrounding Ser(161) is unusual in that residue 158 is histidine. Previously, an arginine located three residues N-terminal to the site of phosphorylation was thought to be critical for the specificity of MAPKAP-K2...
  41. ncbi request reprint Phosphorylation of HSF1 by MAPK-activated protein kinase 2 on serine 121, inhibits transcriptional activity and promotes HSP90 binding
    XiaoZhe Wang
    Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    J Biol Chem 281:782-91. 2006
    ..These experiments indicate a novel mechanism for the regulation of HSF1 by proinflammatory signaling and may permit HSF1 to respond rapidly to extracellular events, permitting optimal physiological regulation...
  42. ncbi request reprint Hypoxia alters biophysical properties of endothelial cells via p38 MAPK- and Rho kinase-dependent pathways
    Steven S An
    Physiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA
    Am J Physiol Cell Physiol 289:C521-30. 2005
    ..Together, these findings suggest that hypoxia differentially regulates endothelial cell contraction and cellular-ECM adhesion...
  43. ncbi request reprint Activation of mitogen-activated protein kinase kinase (MKK) 3 and MKK6 by type I interferons
    Yongzhong Li
    Robert H Lurie Comprehensive Cancer Center and Division of Hematology Oncology, Northwestern University Medical School, 710 North Fairbanks St, Chicago, Illinois 60611, USA
    J Biol Chem 280:10001-10. 2005
    ..Altogether, our findings demonstrate that MKK3 and MKK6 are rapidly activated during engagement of the Type I IFN receptor and play important roles in Type I IFN signaling and the generation of IFN responses...
  44. ncbi request reprint 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
    ....
  45. ncbi request reprint Role of p38alpha Map kinase in Type I interferon signaling
    Yongzhong Li
    Robert H Lurie Comprehensive Cancer Center, Northwestern University Medical School and Lakeside Veterans Administration Medical Center, Chicago, Illinois 60611, USA
    J Biol Chem 279:970-9. 2004
    ..Altogether, our data establish that the p38alpha Map kinase pathway regulates activation of downstream effectors that participate in the induction of IFN-dependent gene transcription, to mediate IFN-responses...
  46. ncbi request reprint 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
    ..Our data provide new evidence for the involvement of MAP kinase pathway in focal ischemic brain injury and suggest that this effect might be associated with the expression of interleukin-1beta in the ischemic brain tissue...
  47. ncbi request reprint Cytoskeletal changes in hypoxic pulmonary endothelial cells are dependent on MAPK-activated protein kinase MK2
    Usamah S Kayyali
    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
    J Biol Chem 277:42596-602. 2002
    ..Taken together these results indicate that hypoxia stimulates the p38-MK2-HSP27 pathway leading to significant alteration in the actin cytoskeleton...
  48. ncbi request reprint 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
    ..moocytogenes. These results indicate an essential role of MK2 in host defense against intracellular bacteria probably via regulation of TNF and IFN-gamma production required for activation of antibacterial effector mechanisms...
  49. ncbi request reprint MAPK-activated protein kinase 2 deficiency in microglia inhibits pro-inflammatory mediator release and resultant neurotoxicity. Relevance to neuroinflammation in a transgenic mouse model of Alzheimer disease
    Ainsley A Culbert
    Neurology and GI Centre of Excellence for Drug Discovery, GlaxoSmithKline Research and Development Limited, New Frontiers Science Park, Third Avenue, Harlow CM19 5AW, Essex, United Kingdom
    J Biol Chem 281:23658-67. 2006
    ..Our data propose a role for MK2 in AD brain pathology, for which neuroinflammation involving cytokines and chemokines and overt neuronal loss have been documented...
  50. 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
    ..This pattern of activation is essential for many NF-kappaB-regulated genes and development of inflammation. Thus, the MK2-HSP27 pathway is an excellent target for therapeutic control of localized inflammatory diseases...
  51. ncbi request reprint 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
    ..Overall, these data provide insight into distinct molecular mechanisms of gene expression regulation by different Toll-like receptor ligands...
  52. ncbi request reprint Activation of p38 mitogen-activated protein kinase contributes to the early cardiodepressant action of tumor necrosis factor
    Mohamed Bellahcene
    Cardiovascular Division, King s College London, The Rayne Institute, St Thomas Hospital, London, United Kingdom
    J Am Coll Cardiol 48:545-55. 2006
    ..The purpose of this study was to determine whether p38 mitogen-activated protein kinase (p38-MAPK) contributes to tumor necrosis factor-alpha (TNFalpha)-induced contractile depression...
  53. ncbi request reprint 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
    ..These studies suggest that MK2-regulated LSP1 phosphorylation is involved in stabilization of F-actin polarization during neutrophil chemotaxis...
  54. 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...
  55. ncbi request reprint 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
    ..Additionally, we show that levels of IL-6 mRNA in paws of mice with CIA correlate with the disease status. These findings suggest that an MK2 inhibitor could be of great therapeutic value to treat inflammatory diseases like RA...
  56. 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
    ..Our data establish the existence of redundant cellular pathways operating downstream of TNF in inflammatory bowel disease, and demonstrate the therapeutic potential of selective kinase blockade in TNF-mediated intestinal pathology...
  57. ncbi request reprint Roles for TAB1 in regulating the IL-1-dependent phosphorylation of the TAB3 regulatory subunit and activity of the TAK1 complex
    Heidi Mendoza
    MRC Protein Phosphorylation Unit, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochem J 409:711-22. 2008
    ....
  58. ncbi request reprint 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
    ..Thus, in DCs, p38 contributes to the activation of all known MK families...
  59. ncbi request reprint Role of heat shock protein 27 in cytoskeletal remodeling of the airway smooth muscle cell
    Steven S An
    Physiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115
    J Appl Physiol (1985) 96:1701-13. 2004
    ..Taken together, these results show that phosphorylated HSP27 favors reduced bead motions that are probably due to stabilization of the actin cytoskeleton...
  60. ncbi request reprint 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
    ..The results suggest that PTEN uropod polarization is F-actin polymerization-dependent and may be through the effect of MK2 on F-actin polarization...
  61. ncbi request reprint 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
    ....
  62. ncbi request reprint P66(ShcA) interacts with MAPKAP kinase 2 and regulates its activity
    Yvonne M Yannoni
    Department of Inflammation, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140 2311, USA
    FEBS Lett 564:205-11. 2004
    ..MK2 is activated with p66(ShcA) co-expression and p66(ShcA) is an in vitro substrate for MK2, further demonstrating their association and suggesting a biological role for p66(Shc) in MK2 activation...
  63. ncbi request reprint 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
    ..Together, our results suggest that MK2 may act to dampen the extent and duration of the p53 response...
  64. pmc Smooth muscle alpha-actin expression and myofibroblast differentiation by TGFbeta are dependent upon MK2
    Anne Marie Sousa
    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
    J Cell Biochem 100:1581-92. 2007
    ..These results indicate that MK2 plays a key role in regulation of smalpha expression, and that targeting MK2 might present a therapeutic approach in managing conditions such as pulmonary fibrosis...
  65. ncbi request reprint 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
    ..TNF-alpha expression is supposably regulated by a posttranscriptional mechanism, whereas IL-6 expression is most likely regulated by transcriptional effects...
  66. ncbi request reprint CXCL12 and C5a trigger cell migration via a PAK1/2-p38alpha MAPK-MAPKAP-K2-HSP27 pathway
    Simon Rousseau
    MRC Protein Phosphorylation Unit, Faculty of Life Sciences, University of Dundee, CIR Building, Dow Street, Dundee DD1 5EH, United Kingdom
    Cell Signal 18:1897-905. 2006
    ..These results demonstrate a general and essential role of the PAK-p38alpha MAPK-MAPKAP-K2-HSP27 signalling pathway in mediating the effects of chemotactic stimuli on cell migration...
  67. 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
    ..Thus, MK2 appears to mediate myofibroblast differentiation, and inhibiting that differentiation might contribute to fibrosis rather than protect against it...