Ripk2

Summary

Gene Symbol: Ripk2
Description: receptor (TNFRSF)-interacting serine-threonine kinase 2
Alias: 2210420D18Rik, CARD3, CARDIAK, CCK, D4Bwg0615e, RICK, RIP2, receptor-interacting serine/threonine-protein kinase 2, tyrosine-protein kinase RIPK2
Species: mouse

Top Publications

  1. ncbi RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs
    Jong Hwan Park
    University of Michigan Medical School, Department of Pathology and Comprehensive Cancer Center, Ann Arbor, MI 48109, USA
    J Immunol 178:2380-6. 2007
  2. doi Receptor-interacting protein-2 deficiency delays macrophage migration and increases intracellular infection during peritoneal dialysis-associated peritonitis
    Michelle L McCully
    FOCIS Centre for Clinical Immunology and Immunotherapeutics, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada
    Am J Nephrol 28:879-89. 2008
  3. pmc The NOD/RIP2 pathway is essential for host defenses against Chlamydophila pneumoniae lung infection
    Kenichi Shimada
    Division of Pediatrics, Infectious Diseases, and Immunology, Cedars Sinai Medical Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
    PLoS Pathog 5:e1000379. 2009
  4. pmc The kinase activity of Rip2 determines its stability and consequently Nod1- and Nod2-mediated immune responses
    Chiara Nembrini
    Institute of Integrative Biology, Molecular Biomedicine, CH 8952 Zurich, Switzerland
    J Biol Chem 284:19183-8. 2009
  5. pmc Nod2 is required for the regulation of commensal microbiota in the intestine
    Tanja Petnicki-Ocwieja
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 106:15813-8. 2009
  6. doi The pattern recognition receptors Nod1 and Nod2 account for neutrophil recruitment to the lungs of mice infected with Legionella pneumophila
    Mariana S Frutuoso
    Department of Cell Biology, University of Sao Paulo, School of Medicine of Ribeirao Preto, FMRP USP, Ribeirao Preto, SP 14049 900, Brazil
    Microbes Infect 12:819-27. 2010
  7. doi The cytosolic sensors Nod1 and Nod2 are critical for bacterial recognition and host defense after exposure to Toll-like receptor ligands
    Yun Gi Kim
    Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Immunity 28:246-57. 2008
  8. pmc Inhibition of RIP2's tyrosine kinase activity limits NOD2-driven cytokine responses
    Justine T Tigno-Aranjuez
    Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    Genes Dev 24:2666-77. 2010
  9. pmc Signaling via the RIP2 adaptor protein in central nervous system-infiltrating dendritic cells promotes inflammation and autoimmunity
    Patrick J Shaw
    Department of Immunology, St Jude Children s Research Hospital, Memphis, TN 38104, USA
    Immunity 34:75-84. 2011
  10. doi Essential role of Rip2 in the modulation of innate and adaptive immunity triggered by Nod1 and Nod2 ligands
    Joao G Magalhaes
    Department of Immunology, University of Toronto, Toronto, Ontario, Canada
    Eur J Immunol 41:1445-55. 2011

Research Grants

  1. RIP2 kinase's function in Innate Immunity
    Derek Abbott; Fiscal Year: 2007

Scientific Experts

  • Hyung Min Kim
  • Laercio R Porto Neto
  • Bindu Sukumaran
  • Li Chung Hsu
  • Sambit K Nanda
  • Jan Boren
  • Chafen Lu
  • Derek Abbott
  • Gabriel Nunez
  • Koichi S Kobayashi
  • Richard A Flavell
  • Thirumala Devi Kanneganti
  • Jong Hwan Park
  • Naohiro Inohara
  • Yun Gi Kim
  • Mizuho Hasegawa
  • Dana J Philpott
  • Kaoru Geddes
  • Kenichi Shimada
  • Chiara Nembrini
  • Fabiane Sonego
  • Tak W Mak
  • Malin C Levin
  • Dario S Zamboni
  • Fernando Q Cunha
  • Stephen E Girardin
  • Douglas R Green
  • Stephen Rubino
  • Paras K Anand
  • Joao G Magalhaes
  • Mohamed Lamkanfi
  • Eike Hollenbach
  • Luigi Franchi
  • Pierre Sicard
  • Sebastien Jacquet
  • Michael Naumann
  • Donghyun Kim
  • Praveen Prakhar
  • Michael P Burrows
  • Poonam R Sharma
  • Katharina Wex
  • Linda Andersson
  • Liangpeng Li
  • Joerg Ermann
  • Hongliang Li
  • Genhong Cheng
  • Antoaneta Belcheva
  • Fera Y Goh
  • Per Fogelstrand
  • Mi Young Jeong
  • Xin An Wang
  • Christopher Lupfer
  • Y J Jeong
  • Paul W Dempsey
  • Shuo Yang
  • Koichi Kobayashi
  • Ulrich Meinzer
  • Hongbo Chi
  • Yun Zhao
  • Catherine Streutker
  • Manuel Koch
  • Silvio M Vieira
  • Sara K B Cassidy
  • Balamayooran Theivanthiran
  • Rune Busk Damgaard
  • Samithamby Jeyaseelan
  • Shanshan Cai
  • Gayathriy Balamayooran
  • Sanjay Batra
  • Gao Sun
  • Maureen A McGargill
  • Patrick J Shaw
  • Theivanthiran Balamayooran
  • Koji Atarashi
  • Garabet Yeretssian
  • Syed Raza Ali
  • Hong Kun Rim
  • Susanne Zach
  • Timothy R Crother
  • Young Sang Koh
  • Maya Saleh
  • Moshe Arditi
  • Shuang Chen
  • Genhong Yao
  • Karine Doiron
  • Kristina A Archer
  • Mariana S Frutuoso
  • Justine T Tigno-Aranjuez
  • Lars Eckmann
  • Amlan Biswas

Detail Information

Publications87

  1. ncbi RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs
    Jong Hwan Park
    University of Michigan Medical School, Department of Pathology and Comprehensive Cancer Center, Ann Arbor, MI 48109, USA
    J Immunol 178:2380-6. 2007
    b>RICK is a kinase that has been implicated in Nod1 and Nod2 signaling. In addition, RICK has been proposed to mediate TLR signaling in that its absence confers reduced responses to certain bacterial products such as LPS...
  2. doi Receptor-interacting protein-2 deficiency delays macrophage migration and increases intracellular infection during peritoneal dialysis-associated peritonitis
    Michelle L McCully
    FOCIS Centre for Clinical Immunology and Immunotherapeutics, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada
    Am J Nephrol 28:879-89. 2008
    Early upregulation of receptor-interacting protein-2 (RIP2) expression during peritoneal dialysis (PD)-associated peritonitis correlates with a favorable clinical outcome, while failure to upregulate RIP2 correlates with a protracted ..
  3. pmc The NOD/RIP2 pathway is essential for host defenses against Chlamydophila pneumoniae lung infection
    Kenichi Shimada
    Division of Pediatrics, Infectious Diseases, and Immunology, Cedars Sinai Medical Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
    PLoS Pathog 5:e1000379. 2009
    Here we investigated the role of the Nod/Rip2 pathway in host responses to Chlamydophila pneumoniae-induced pneumonia in mice. Rip2(-/-) mice infected with C...
  4. pmc The kinase activity of Rip2 determines its stability and consequently Nod1- and Nod2-mediated immune responses
    Chiara Nembrini
    Institute of Integrative Biology, Molecular Biomedicine, CH 8952 Zurich, Switzerland
    J Biol Chem 284:19183-8. 2009
    Rip2 (RICK, CARD3) has been identified as a key effector molecule downstream of the pattern recognition receptors, Nod1 and Nod2; however, its mechanism of action remains to be elucidated...
  5. pmc Nod2 is required for the regulation of commensal microbiota in the intestine
    Tanja Petnicki-Ocwieja
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 106:15813-8. 2009
    ..Therefore, Nod2 and intestinal commensal bacterial flora maintain a balance by regulating each other through a feedback mechanism. Dysfunction of Nod2 results in a break-down of this homeostasis...
  6. doi The pattern recognition receptors Nod1 and Nod2 account for neutrophil recruitment to the lungs of mice infected with Legionella pneumophila
    Mariana S Frutuoso
    Department of Cell Biology, University of Sao Paulo, School of Medicine of Ribeirao Preto, FMRP USP, Ribeirao Preto, SP 14049 900, Brazil
    Microbes Infect 12:819-27. 2010
    ..By using mice deficient for Nod1, Nod2, and Rip2, we found that these receptors accounted for NE recruitment to the lungs of infected mice...
  7. doi The cytosolic sensors Nod1 and Nod2 are critical for bacterial recognition and host defense after exposure to Toll-like receptor ligands
    Yun Gi Kim
    Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Immunity 28:246-57. 2008
    ..revealed that innate immune responses induced by bacterial infection relied on Nod1 and Nod2 and their adaptor RICK in macrophages pretreated with TLR ligands but not in naive macrophages...
  8. pmc Inhibition of RIP2's tyrosine kinase activity limits NOD2-driven cytokine responses
    Justine T Tigno-Aranjuez
    Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    Genes Dev 24:2666-77. 2010
    ..sarcoidosis susceptibility protein NOD2 (nucleotide oligomerization domain protein 2) binds to the protein kinase RIP2 (receptor-interacting protein 2) to coordinate NF-κB (nuclear factor κ B)-mediated cytokine responses...
  9. pmc Signaling via the RIP2 adaptor protein in central nervous system-infiltrating dendritic cells promotes inflammation and autoimmunity
    Patrick J Shaw
    Department of Immunology, St Jude Children s Research Hospital, Memphis, TN 38104, USA
    Immunity 34:75-84. 2011
    ..NOD1 and NOD2 and their common downstream adaptor molecule, receptor interacting protein 2 (RIP2; also known as RIPK2 and RICK)...
  10. doi Essential role of Rip2 in the modulation of innate and adaptive immunity triggered by Nod1 and Nod2 ligands
    Joao G Magalhaes
    Department of Immunology, University of Toronto, Toronto, Ontario, Canada
    Eur J Immunol 41:1445-55. 2011
    ..Here, we investigated the role of Rip2, the adaptor for Nod1- and Nod2-dependent signaling, in multiple aspects of the host response to muramyl peptides ..
  11. ncbi NOD2 pathway activation by MDP or Mycobacterium tuberculosis infection involves the stable polyubiquitination of Rip2
    Yibin Yang
    Department of Pathology, Case Western University School of Medicine, Cleveland, Ohio 44106, USA
    J Biol Chem 282:36223-9. 2007
    The Rip2 kinase contains a caspase recruitment domain and has been implicated in the activation of the transcriptional factor NF-kappaB downstream of Toll-like receptors, Nod-like receptors, and the T cell receptor...
  12. ncbi Nod1/RICK and TLR signaling regulate chemokine and antimicrobial innate immune responses in mesothelial cells
    Jong Hwan Park
    Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA
    J Immunol 179:514-21. 2007
    ..the chemokines CXCL1 and CCL2 as well as expression of inducible NO synthase and such responses required the kinase RICK. Mesothelial cells also produced chemokines in response to TLR2, TLR3, TLR4, and TLR5 agonists, but unlike that ..
  13. pmc TLR2 and RIP2 pathways mediate autophagy of Listeria monocytogenes via extracellular signal-regulated kinase (ERK) activation
    Paras K Anand
    Department of Immunology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Biol Chem 286:42981-91. 2011
    ..Here, we show that macrophages deficient in the TLR2 and NOD/RIP2 pathway display defective autophagy induction in response to L. monocytogenes...
  14. ncbi Recognition of cytosolic DNA activates an IRF3-dependent innate immune response
    Daniel B Stetson
    Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Immunity 24:93-103. 2006
    ..These findings define an innate immune response to DNA linked to type I interferon production...
  15. ncbi The Crohn's disease protein, NOD2, requires RIP2 in order to induce ubiquitinylation of a novel site on NEMO
    Derek W Abbott
    Division of Gastrointestinal Pathology, Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Curr Biol 14:2217-27. 2004
    ..NOD2 can both strongly activate and negatively attenuate NF-kB signaling. The biochemical mechanism for this dual function of NOD2 is unknown...
  16. ncbi RICK, a novel protein kinase containing a caspase recruitment domain, interacts with CLARP and regulates CD95-mediated apoptosis
    N Inohara
    Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Biol Chem 273:12296-300. 1998
    Signaling through the CD95/Fas/APO-1 death receptor plays a critical role in the homeostasis of the immune system. RICK, a novel protein kinase that regulates CD95-mediated apoptosis was identified and characterized...
  17. ncbi Involvement of receptor-interacting protein 2 in innate and adaptive immune responses
    Arnold i Chin
    Molecular Biology Institute, University of California, Los Angeles, California 90095, USA
    Nature 416:190-4. 2002
    ..To understand the physiological role of receptor-interacting protein 2 (Rip2), also known as RICK and CARDIAK, we generated mice with a targeted disruption of the gene coding for Rip2...
  18. ncbi RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems
    Koichi Kobayashi
    Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nature 416:194-9. 2002
    ..we show that the caspase recruitment domain (CARD)-containing serine/threonine kinase Rip2 (also known as RICK, CARDIAK, CCK and Ripk2) transduces signals from receptors of both immune responses...
  19. ncbi Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf
    Sanjeev Mariathasan
    Molecular Oncology Department, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nature 430:213-8. 2004
    ..The adaptors ASC, Ipaf and RIP2 have each been proposed to regulate caspase-1 (also called interleukin (IL)-1 converting enzyme), which is ..
  20. pmc Induction of microRNA-155 is TLR- and type IV secretion system-dependent in macrophages and inhibits DNA-damage induced apoptosis
    Manuel Koch
    Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin 10117, Germany
    Proc Natl Acad Sci U S A 109:E1153-62. 2012
    ..pylori pathogenicity factor, the T4SS, in the up-regulation of miR-155 in BMMs. We propose the antiapoptotic effects of miR-155 could enhance macrophage resistance to apoptosis induced by DNA damage during H. pylori infection...
  21. pmc MyD88-, but not Nod1- and/or Nod2-deficient mice, show increased susceptibility to polymicrobial sepsis due to impaired local inflammatory response
    Fabiane Sonego
    Faculdade de Medicina de Ribeirao Preto, Departamento de Farmacologia, Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo, Brasil
    PLoS ONE 9:e103734. 2014
    ..during CLP-induced septic peritonitis because these events were similar in wild-type, Nod1-, Nod2-, Nod1/Nod2- and Rip2-deficient mice. Consequently, the local and systemic bacterial loads were not altered...
  22. pmc An Islet-Targeted Genome-Wide Association Scan Identifies Novel Genes Implicated in Cytokine-Mediated Islet Stress in Type 2 Diabetes
    Poonam R Sharma
    Department of Medicine P R S, E A D, J W R, C S N, Center for Public Health Genomics A J M, S S R, and Department of Chemistry E A D, University of Virginia, Charlottesville, Virginia 22904 Department of Biochemistry N D P, Center for Genomics and Personalized Medicine Research N D P, Center for Diabetes Research N D P, Center for Public Health Genomics C D L, N D P, L E W, Department of Biostatistical Sciences C D L, and Division of Public Health Sciences L E W, Wake Forest School of Medicine, Winston Salem, North Carolina 27157 Department of Physiology and Biophysics R M W, Department of Preventive Medicine, and USC Diabetes and Obesity Research Institute R M W, Keck School of Medicine of University of Southern California, Los Angeles, California 90033 and Institute for Translational Genomics and Population Sciences K D T and Department of Pediatrics K D T, Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, Torrance, California 90502
    Endocrinology 156:3147-56. 2015
    ..3), F13a1 (6p25.3), Klhl6 (3q27.1), Nid1 (1q42.3), Pamr1 (11p13), Ripk2 (8q21.3), and Steap4 (7q21.12)...
  23. pmc Control of NOD2 and Rip2-dependent innate immune activation by GEF-H1
    Yun Zhao
    Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Inflamm Bowel Dis 18:603-12. 2012
    ..Genetic variants of nucleotide-binding oligomerization domain 2 (NOD2) lead to aberrant microbial recognition and can cause chronic inflammatory diseases in patients with Crohn's disease (CD)...
  24. doi Gut microbial metabolism drives transformation of MSH2-deficient colon epithelial cells
    Antoaneta Belcheva
    Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada
    Cell 158:288-99. 2014
    ..These data thereby provide an explanation for the interaction between microbiota, diet, and mismatch repair deficiency in CRC induction. PAPERCLIP:..
  25. doi Rip2 modifies VEGF-induced signalling and vascular permeability in myocardial ischaemia
    Linda Andersson
    Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, 413 45 Goteborg, Sweden
    Cardiovasc Res 107:478-86. 2015
    ..In this study, we investigated the role of receptor-interacting protein 2 (Rip2) in VEGF signalling and myocardial ischaemia/reperfusion injury.
  26. pmc Microbiota regulates type 1 diabetes through Toll-like receptors
    Michael P Burrows
    Department of Pathology and Committee on Immunology, University of Chicago, Chicago, IL 60637
    Proc Natl Acad Sci U S A 112:9973-7. 2015
    ..Our results support the balanced signal hypothesis, in which microbes provide signals that both promote and inhibit autoimmunity by signaling through different receptors, including receptors of the TLR family. ..
  27. doi Saengmaeksan inhibits inflammatory mediators by suppressing RIP-2/caspase-1 activation
    Mi Young Jeong
    College of Korean Medicine, Institute of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
    Immunopharmacol Immunotoxicol 35:241-50. 2013
    ..In this study, we attempt to determine the effects of SMS on lipopolysaccharide (LPS)-induced inflammatory responses in mouse peritoneal macrophages...
  28. pmc Ac2PIM-responsive miR-150 and miR-143 target receptor-interacting protein kinase 2 and transforming growth factor beta-activated kinase 1 to suppress NOD2-induced immunomodulators
    Praveen Prakhar
    From the Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, Karnataka, India and
    J Biol Chem 290:26576-86. 2015
    ..microRNA expression profiling identified Ac2PIM-responsive miR-150 and miR-143 to target NOD2 signaling adaptors, RIP2 and TAK1, respectively...
  29. doi Regulatory role of CARD3 in left ventricular remodelling and dysfunction after myocardial infarction
    Liangpeng Li
    Department of Thoracic and Cardiovascular Surgery, Nanjing Hospital affiliated to Nanjing Medical University, Changle Road 68, Nanjing, 210006, Jiangsu, People s Republic of China
    Basic Res Cardiol 110:56. 2015
    Caspase activation and recruitment domain 3 (CARD3) is a caspase recruitment domain (CARD)-containing serine/threonine kinase and plays a pivotal role in apoptosis, immunity, tissue development and proliferation...
  30. pmc Receptor-Interacting Protein Kinase-2 Inhibition by CYLD Impairs Antibacterial Immune Responses in Macrophages
    Katharina Wex
    Institute of Medical Microbiology and Hospital Hygiene, Otto von Guericke University Magdeburg, Magdeburg, Germany
    Front Immunol 6:650. 2015
    ..recognizes bacterial muramyl dipeptide and binds, subsequently, to receptor-interacting serine/threonine kinase 2 (RIPK2), which activates immune responses via the nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) ..
  31. doi RIP2/RICK-dependent cytokine production upon Yersinia enterocolitica infection in macrophages with TLR4 deficiency
    Y J Jeong
    Department of Biochemistry, College of Medicine, Konyang University, Daejeon, Republic of Korea
    Scand J Immunol 78:401-7. 2013
    Receptor-interacting protein 2 (RIP2) is a caspase recruitment domain (CARD)-containing serine/threonine kinase that is activated by NOD1 or NOD2 recognition of their ligands and essential for the activation of NF-κB and mitogen-..
  32. pmc Nod2-mediated recognition of the microbiota is critical for mucosal adjuvant activity of cholera toxin
    Donghyun Kim
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA
    Nat Med 22:524-30. 2016
    ..These results show a role for the microbiota and the intracellular receptor Nod2 in promoting the mucosal adjuvant activity of CT. ..
  33. pmc Nod/Ripk2 signaling in dendritic cells activates IL-17A-secreting innate lymphoid cells and drives colitis in T-bet-/-.Rag2-/- (TRUC) mice
    Joerg Ermann
    Division of Rheumatology, Immunology, and Allergy, Brigham and Women s Hospital, Boston, MA 02115 Harvard Medical School, Boston, MA 02115
    Proc Natl Acad Sci U S A 111:E2559-66. 2014
    ..by nucleotide-binding oligomerization domain containing (Nod)/receptor-interacting serine-threonine kinase 2 (Ripk2) signals in DCs...
  34. pmc Caspase recruitment domain-containing sensors and adaptors in intestinal innate immunity
    Petr Hruz
    Department of Medicine, University of California, San Diego, La Jolla, California, USA
    Curr Opin Gastroenterol 24:108-14. 2008
    ..The present review discusses the physiological functions of selected caspase recruitment domain (CARD)-containing sensor and adaptor proteins and their role in the pathogenesis of intestinal diseases...
  35. doi Pellino3 ubiquitinates RIP2 and mediates Nod2-induced signaling and protective effects in colitis
    Shuo Yang
    Institute of Immunology, Department of Biology, National University of Ireland Maynooth, Ireland
    Nat Immunol 14:927-36. 2013
    ..Pellino3 directly bound to the kinase RIP2 and catalyzed its ubiquitination...
  36. doi Receptor-interacting protein 2 gene silencing attenuates allergic airway inflammation
    Fera Y Goh
    Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore 119228
    J Immunol 191:2691-9. 2013
    Persistent activation of NF-κB has been associated with the development of asthma. Receptor-interacting protein 2 (Rip2) is a transcriptional product of NF-κB activation...
  37. doi Joint NOD2/RIPK2 signaling regulates IL-17 axis and contributes to the development of experimental arthritis
    Silvio M Vieira
    Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo 14049 900, Brazil
    J Immunol 188:5116-22. 2012
    ..was generated in wild-type, NOD1(-/-), NOD2(-/-), or receptor-interacting serine-threonine kinase 2(-/-) (RIPK2(-/-)) immunized mice challenged intra-articularly with methylated BSA...
  38. doi The RIPK2 gene: a positional candidate for tick burden supported by genetic associations in cattle and immunological response of knockout mouse
    Laercio R Porto Neto
    CSIRO Livestock Industries, Queensland Bioscience Precinct, St Lucia, QLD, Australia
    Immunogenetics 64:379-88. 2012
    ..on BTA14 at ~72 Mb distal to the centromere, near the gene receptor-interacting serine-threonine kinase 2 (RIPK2)...
  39. doi Yersinia pseudotuberculosis effector YopJ subverts the Nod2/RICK/TAK1 pathway and activates caspase-1 to induce intestinal barrier dysfunction
    Ulrich Meinzer
    Universite Paris Diderot, Paris, France
    Cell Host Microbe 11:337-51. 2012
    ..but not the catalytically inactive mutant YopJ(C172A), acetylates critical sites in the activation loops of the RICK and TAK1 kinases, which are central mediators of Nod2 signaling, and decreases the affinity of Nod2 for RICK...
  40. doi Alcohol-fermented soybean increases the expression of receptor-interacting protein 2 and IκB kinase β in mouse peritoneal macrophages
    Hong Kun Rim
    Department of Pharmacology, College of Oriental Medicine, Kyung Hee University, Seoul, Korea
    J Med Food 14:1181-9. 2011
    ..used in combination with rIFN-γ, there was a co-operative activation of NF-κB and receptor-interacting protein 2 (Rip2)/IκB kinase (IKK)-β...
  41. pmc NOD2 signaling contributes to host defense in the lungs against Escherichia coli infection
    Balamayooran Theivanthiran
    Laboratory of Lung Biology, Department of Pathobiological Sciences and Center for Experimental Infectious Disease Research, Harvard Medical School, Boston, Massachusetts, USA
    Infect Immun 80:2558-69. 2012
    ..Although we demonstrated that RIP2 is important for host defense in the lungs against Escherichia coli, the individual roles of NOD1 and NOD2 in ..
  42. doi The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in inflammation and innate immunity
    Rune Busk Damgaard
    Department of Disease Biology, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, 2200 Copenhagen, Denmark
    Mol Cell 46:746-58. 2012
    ..We find that XIAP ubiquitylates RIPK2 and recruits the linear ubiquitin chain assembly complex (LUBAC) to NOD2...
  43. pmc Receptor interacting protein-2 contributes to host defense against Anaplasma phagocytophilum infection
    Bindu Sukumaran
    Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
    FEMS Immunol Med Microbiol 66:211-9. 2012
    ..phagocytophilum, are less understood. We herein report an unexpected role for Receptor interacting protein-2 (Rip2), the adaptor protein for the Nod-like receptors (NLRs), Nod1/Nod2, in the host immune response against A...
  44. pmc Membrane damage during Listeria monocytogenes infection triggers a caspase-7 dependent cytoprotective response
    Sara K B Cassidy
    Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America
    PLoS Pathog 8:e1002628. 2012
    ..not require caspase-1 or key adaptors of the primary pathways of innate immune signaling in this infection, ASC, RIP2 and MyD88...
  45. doi CARD3 deficiency exacerbates diet-induced obesity, hepatosteatosis, and insulin resistance in male mice
    Xin An Wang
    Department of Cardiology, Renmin Hospital of Wuhan University, and Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China
    Endocrinology 154:685-97. 2013
    Caspase activation and recruitment domain 3 (CARD3) is a 61-kDa protein kinase with an N-terminal serine/threonine kinase domain and a C-terminal CARD...
  46. pmc Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection
    Christopher Lupfer
    Department of Immunology, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Nat Immunol 14:480-8. 2013
    NOD2 receptor and the cytosolic protein kinase RIPK2 regulate NF-κB and MAP kinase signaling during bacterial infections, but the role of this immune axis during viral infections has not been addressed...
  47. pmc Signal transduction protein array analysis links LRRK2 to Ste20 kinases and PKC zeta that modulate neuronal plasticity
    Susanne Zach
    Boehringer Ingelheim Pharma GmbH and Co KG, CNS Research, Biberach an der Riss, Germany
    PLoS ONE 5:e13191. 2010
    ..LRRK2 has been linked to the mitogen-activated protein kinase kinase kinase family and the receptor-interacting protein kinases based on sequence similarity within the kinase domain and in vitro substrate phosphorylation...
  48. ncbi MDP-induced interleukin-1beta processing requires Nod2 and CIAS1/NALP3
    Qilin Pan
    Department of Immunology, The Scripps Research Institute, La Jolla, California, USA
    J Leukoc Biol 82:177-83. 2007
    ..showing that MDP-induced IL-1beta release requires Nod2 and CIAS1/NALP3 as well as receptor-interacting protein-2 (Rip2), apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), and caspase-..
  49. ncbi Pannexin-1-mediated recognition of bacterial molecules activates the cryopyrin inflammasome independent of Toll-like receptor signaling
    Thirumala Devi Kanneganti
    Department of Pathology, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Immunity 26:433-43. 2007
    ..These results provide evidence for cytosolic delivery and sensing of bacterial molecules as a unifying model for caspase-1 activation and position pannexin-1 as a mechanistic link between bacterial stimuli and the cryopyrin inflammasome...
  50. pmc Caspase recruitment domain protein 6 is a microtubule-interacting protein that positively modulates NF-kappaB activation
    Almut Dufner
    Campbell Family Institute for Breast Cancer Research, Toronto, ON, Canada M5G 2C1
    Proc Natl Acad Sci U S A 103:988-93. 2006
    ..with receptor-interacting protein (RIP)-like interacting caspase-like apoptosis regulatory protein kinase (RICK), a CARD-containing member of the RIP family of protein kinases...
  51. ncbi Inhibition of RICK/nuclear factor-kappaB and p38 signaling attenuates the inflammatory response in a murine model of Crohn disease
    Eike Hollenbach
    Institute of Experimental Internal Medicine, Department of Gastroenterology, Hepatology and Infectiology, Otto von Guericke University, Magdeburg D 39120, Germany
    J Biol Chem 280:14981-8. 2005
    ..of NF-kappaB activation revealed that Rip-like interacting caspase-like apoptosis-regulatory protein kinase (RICK), a key component of a pathway leading to NF-kappaB induction, is also strongly inhibited by SB203580...
  52. ncbi Participation of Rip2 in lipopolysaccharide signaling is independent of its kinase activity
    Chafen Lu
    Millennium Pharmaceuticals, Inc, Cambridge, Massachusetts 02139, USA
    J Biol Chem 280:16278-83. 2005
    Rip2 (Rick, Cardiak, CCK2, and CARD3) is a serine/threonine kinase containing a caspase recruitment domain (CARD) at the C terminus...
  53. ncbi Immune activation of type I IFNs by Listeria monocytogenes occurs independently of TLR4, TLR2, and receptor interacting protein 2 but involves TNFR-associated NF kappa B kinase-binding kinase 1
    Ryan M O'Connell
    Department of Microbiology, Immunology and Molecular Genetics, University of California, CA 90095, USA
    J Immunol 174:1602-7. 2005
    ..Additionally, we provide evidence that both the LM- and TLR-dependent pathways converge at TBK1 to activate type I IFNs, highlighting the central role of this molecule in modulating type I IFNs in host defense and disease...
  54. ncbi Inhibition of p38 MAP kinase- and RICK/NF-kappaB-signaling suppresses inflammatory bowel disease
    Eike Hollenbach
    Institute of Experimental Internal Medicine, Otto von Guericke University, Magdeburg, Germany
    FASEB J 18:1550-2. 2004
    ..basis of NF-kappaB activation revealed that Rip-like interacting caspase-like apoptosis-regulatory protein kinase (RICK), a key component of a pathway leading to NF-kappaB induction, is also strongly inhibited by SB203580...
  55. pmc Tissue-specific down-regulation of RIPK 2 in Mycobacterium leprae-infected nu/nu mice
    Byoung Chul Kim
    Institute of Hansen s Disease, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, South Korea
    Mediators Inflamm 13:51-2. 2004
    ..leprae were down-regulated in the skin but were up-regulated in the liver. Overall, this suggests that regulation of RIPK 2 expression is tissue-specifically associated with M. leprae infection...
  56. pmc Fundamental role of the Rip2/caspase-1 pathway in hypoxia and ischemia-induced neuronal cell death
    Wen Hua Zhang
    Department of Neurosurgery, Qilu Hospital, Shandong University, 250012, People s Republic of China
    Proc Natl Acad Sci U S A 100:16012-7. 2003
    ..Furthermore, we demonstrate that Rip2/Cardiak/Rick is a stress-inducible upstream modulator of pro-caspase-1 apoptotic activation...
  57. ncbi Rip2 participates in Bcl10 signaling and T-cell receptor-mediated NF-kappaB activation
    Astrid A Ruefli-Brasse
    Department of Molecular Oncology, Genentech, Inc, South San Francisco, California 94080, USA
    J Biol Chem 279:1570-4. 2004
    ..Herein we demonstrate that Rip2, a caspase recruitment domain (CARD)-containing serine/threonine kinase, plays an important role in this cascade ..
  58. ncbi Protein kinase C-associated kinase (PKK) mediates Bcl10-independent NF-kappa B activation induced by phorbol ester
    Akihiro Muto
    Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Biol Chem 277:31871-6. 2002
    ..domain of PKK is highly homologous to that of two mediators of nuclear factor-kappa B (NF-kappa B) activation, RICK and RIP, but these related kinases have different C-terminal domains for binding to upstream factors...
  59. pmc Type I interferon signaling is required for activation of the inflammasome during Francisella infection
    Thomas Henry
    Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA
    J Exp Med 204:987-94. 2007
    ..This connection underscores the importance of the cytosolic recognition of pathogens and highlights how multiple innate immunity pathways interact before commitment to critical host responses...
  60. ncbi cDNA sequence, map, and expression of the murine homolog of GTBP, a DNA mismatch repair gene
    A Corradi
    Department of Biological and Technological Research DIBIT, San Raffaele Scientific Institute, Via Olgettina 58, Milan, 20132, Italy
    Genomics 36:288-95. 1996
    ..Studies of the expression of Gtmbp suggest that its regulated transcription is tightly linked to the level of DNA replication, consistent with the protein's DNA proofreading function...
  61. pmc Coordinated regulation of Toll-like receptor and NOD2 signaling by K63-linked polyubiquitin chains
    Derek W Abbott
    Department of Pathology, Case Western Reserve University School of Medicine, Room 5123 Wolstein Research Building, Cleveland, OH 44106, and Department of Pathology, Brigham and Women s Hospital, Boston, MA, USA
    Mol Cell Biol 27:6012-25. 2007
    ..We further show that TRAF6 and NOD2/RIP2 share the same biochemical machinery (transforming growth factor beta-activated kinase 1 [TAK1]/TAB/Ubc13) to ..
  62. ncbi RIP2 contributes to Nod signaling but is not essential for T cell proliferation, T helper differentiation or TLR responses
    Håkan T L Hall
    Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Department of Immunology, University of Toronto, Toronto, Canada
    Eur J Immunol 38:64-72. 2008
    Receptor-interacting protein 2 (RIP2), also known as CARDIAK and RICK, has been reported to play a role in both adaptive T cell responses and innate immunity as a mediator in TLR signaling and nucleotide-binding oligomerization domain (..
  63. pmc RICK promotes inflammation and lethality after gram-negative bacterial infection in mice stimulated with lipopolysaccharide
    Jong Hwan Park
    Department of Pathology, University of Michigan Medical School, and University of Michigan Comprehensive Cancer Center, 1500 E Medical Center Dr, Ann Arbor, MI 48109, USA
    Infect Immun 77:1569-78. 2009
    b>RICK (receptor-interacting protein-like interacting caspase-like apoptosis regulatory protein kinase), a serine-threonine kinase, functions downstream of the pattern recognition receptors Nod1 and Nod2 to mediate NF-kappaB and mitogen-..
  64. pmc Pharmacological postconditioning effect of muramyl dipeptide is mediated through RIP2 and TAK1
    Pierre Sicard
    King s College London British Heart Foundation Centre of Research Excellence, The Cardiovascular Division, The Rayne Institute, St Thomas Hospital, Lambeth Palace Road, London SE1 7EH, UK
    Cardiovasc Res 83:277-84. 2009
    ..Receptor activation leads to intracellular signals through receptor interacting protein-2 (RIP2) and tumour growth factor-beta-activated kinase-1 (TAK1)...
  65. pmc A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide
    Li Chung Hsu
    Departments of Pharmacology and Pathology, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 105:7803-8. 2008
    ..Thus, NOD2 plays a key role in the B. anthracis-induced inflammatory response by being a critical mediator of IL-1beta secretion...
  66. doi Cellular inhibitors of apoptosis cIAP1 and cIAP2 are required for innate immunity signaling by the pattern recognition receptors NOD1 and NOD2
    Mathieu J M Bertrand
    Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
    Immunity 30:789-801. 2009
    ..Here, we show that administration of MDP protected wild-type but not Ripk2(-/-) or Birc3(-/-) mice from colitis, confirming the role of the cIAPs in NOD2 signaling in vivo...
  67. doi Effective T-cell immune responses in the absence of the serine/threonine kinase RIP2
    Chiara Nembrini
    Institute of Integrative Biology, Molecular Biomedicine, ETH Zurich, Swiss Federal Institute of Technology, Wagistrasse 27, CH 8952 Zurich Schlieren, Switzerland
    Microbes Infect 10:522-30. 2008
    The serine/threonine kinase RIP2 has been reported to be essential for Nod1 and Nod2 mediated cell activation, and has been suggested to play a role in the signaling cascade downstream of the T-cell receptor...
  68. pmc The role of RIP2 in p38 MAPK activation in the stressed heart
    Sebastien Jacquet
    Cardiovascular Division, King s College London, The Rayne Institute, St Thomas Hospital, London SE1 7EH, United Kingdom
    J Biol Chem 283:11964-71. 2008
    ..Studies in non-cardiac tissue have shown receptor-interacting protein 2 (RIP2) lies upstream of p38 MAPK, is SB203580-sensitive and ischemia-responsive, and aggravates ischemic injury...
  69. doi Phenotype and functions of spleen dendritic cells in RICK-knockout mice
    Genhong Yao
    Immunology and Reproductive Biology Lab, Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, PRChina
    Int Immunopharmacol 10:130-3. 2010
    b>RICK (receptor-interacting caspase-like apoptosis-regulatory kinase), a protein kinase, promotes nuclear factor kappa B and caspase activation. Herein, in order to further learn the immune role of RICK, its gene in mice was knocked out...
  70. pmc Transitions in oral and intestinal microflora composition and innate immune receptor-dependent stimulation during mouse development
    Mizuho Hasegawa
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Infect Immun 78:639-50. 2010
    ..of the intestinal microflora was still intact in NOD1-, NOD2-, TLR2-, TLR4-, TLR5-, TLR9-, TLR11-, ASC-, or RICK-deficient cells but still relied on the adaptor MyD88...
  71. pmc Cooperation between multiple microbial pattern recognition systems is important for host protection against the intracellular pathogen Legionella pneumophila
    Kristina A Archer
    Section of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA
    Infect Immun 78:2477-87. 2010
    ..b>Rip2 and Naip5/NLRC4 signaling was found to contribute to the innate immune response generated against L...
  72. pmc MyD88-dependent signaling contributes to host defense against ehrlichial infection
    Young Sang Koh
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts, United States of America
    PLoS ONE 5:e11758. 2010
    ....
  73. pmc Nod1 and Nod2 regulation of inflammation in the Salmonella colitis model
    Kaoru Geddes
    Department of Immunology, University of Toronto, Toronto, Ontario M6G 2T6, Canada
    Infect Immun 78:5107-15. 2010
    ..to the pathology, and all phenotypes were recapitulated in mice deficient for the signaling adaptor protein Rip2. However, the influence of Rip2 was strictly dependent on infection conditions that favored expression of the ..
  74. doi RIP2 is required for NOD signaling but not for Th1 cell differentiation and cellular allograft rejection
    T Fairhead
    The FOCIS Centre for Clinical Immunology and Immunotherapeutics, Robarts Research Institute, London, Ontario, Canada
    Am J Transplant 8:1143-50. 2008
    Two previous reports that receptor-interacting protein (RIP)-2 knockout (RIP2-/-) mice had defective nuclear factor-kappa B (NF-kappaB) signaling and T helper (Th)1 immune responses had led us to believe that this putative serine-..
  75. pmc RIP2-mediated LKB1 deletion causes axon degeneration in the spinal cord and hind-limb paralysis
    Gao Sun
    Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, UK
    Dis Model Mech 4:193-202. 2011
    ..We thus define LKB1 as an intrinsic suppressor of axon degeneration and a possible target for strategies that can reverse this process...
  76. pmc Induction of colonic regulatory T cells by indigenous Clostridium species
    Koji Atarashi
    Department of Immunology, Graduate School of Medicine, University of Tokyo, Tokyo 113 0033, Japan
    Science 331:337-41. 2011
    ....
  77. pmc A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation
    Mizuho Hasegawa
    Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA
    EMBO J 27:373-83. 2008
    ..Nod1 and Nod2 stimulation activates NF-kappaB through RICK, a caspase-recruitment domain-containing kinase...
  78. ncbi RIP2 regulates growth and differentiation of normal myoblasts and of rhabdomyosarcoma cells
    Svenja Ehlers
    Charite University Medicine Berlin, Institute of Physiology, Arnimallee 22, D 14195 Berlin, Germany
    Eur J Cell Biol 87:163-72. 2008
    b>RIP2 is an important regulator of myoblast proliferation and differentiation...
  79. doi Non-apoptotic role of BID in inflammation and innate immunity
    Garabet Yeretssian
    Department of Medicine, McGill University, Montreal, Quebec H3G 0B1, Canada
    Nature 474:96-9. 2011
    ..Our results define a novel role of BID in inflammation and immunity independent of its apoptotic function, furthering the mounting evidence of evolutionary conservation between the mechanisms of apoptosis and immunity...
  80. pmc Polyubiquitin binding to ABIN1 is required to prevent autoimmunity
    Sambit K Nanda
    Medical Research Council Protein Phosphorylation Unit, Sir James Black Centre, University of Dundee, Dundee DD1 5EH, Scotland, UK
    J Exp Med 208:1215-28. 2011
    ..The mutant B cells also proliferated more rapidly in response to TLR ligands. Our results indicate that the interaction of ABIN1 with polyubiquitin is required to limit the activation of TLR-MyD88 pathways and prevent autoimmunity...
  81. pmc Anthrax toxin induces macrophage death by p38 MAPK inhibition but leads to inflammasome activation via ATP leakage
    Syed Raza Ali
    Laboratory of Signal Transduction, Department of Pharmacology, University of California, San Diego, La Jolla, California, USA
    Immunity 35:34-44. 2011
    ..Prevention of cell death or ATP release through constitutive p38 or AKT activation interfered with inflammasome activation and IL-1β production, thereby compromising antimicrobial immunity...
  82. pmc Caspase-1 dependent IL-1β secretion is critical for host defense in a mouse model of Chlamydia pneumoniae lung infection
    Kenichi Shimada
    Division of Pediatrics Infectious Disease and Immunology, Cedars Sinai Medical Center and David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States of America
    PLoS ONE 6:e21477. 2011
    ..Interestingly, Caspase-1 activation during CP infection occurs with mitochondrial dysfunction indicating a possible mechanism involving the mitochondria for CP-induced inflammasome activation...
  83. pmc Receptor-interacting protein 2 controls pulmonary host defense to Escherichia coli infection via the regulation of interleukin-17A
    Theivanthiran Balamayooran
    Laboratory of Lung Biology, Department of Pathobiological Sciences and Center for Experimental Infectious Disease Research, Louisiana State University LSU, Baton Rouge, Louisiana 708031, USA
    Infect Immun 79:4588-99. 2011
    ..coli infection model using mice deficient in the gene coding for the NLR adaptor, receptor-interacting protein 2 (RIP2). RIP2(-/-) mice with E...
  84. pmc MyD88-mediated signals induce the bactericidal lectin RegIII gamma and protect mice against intestinal Listeria monocytogenes infection
    Katharina Brandl
    Infectious Diseases Service, Department of Medicine, Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Exp Med 204:1891-900. 2007
    ..Our findings support a model of MyD88-mediated epithelial conditioning that protects the intestinal mucosa against bacterial invasion by inducing RegIII gamma...
  85. doi Rip2 deficiency leads to increased atherosclerosis despite decreased inflammation
    Malin C Levin
    Department of Molecular and Clinical Medicine Wallenberg Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden
    Circ Res 109:1210-8. 2011
    ..Receptor-interacting protein 2 (Rip2) is a serine/threonine kinase that is involved in multiple nuclear factor-κB (NFκB) activation pathways, ..

Research Grants1

  1. RIP2 kinase's function in Innate Immunity
    Derek Abbott; Fiscal Year: 2007
    ..Although critical, this specificity in signal transduction is poorly understood. The adapter protein kinase RIP2 may mediate a portion of this specificity...