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
Products:     Ripk2

Top Publications

  1. Petnicki Ocwieja T, Hrncir T, Liu Y, Biswas A, Hudcovic T, Tlaskalova Hogenova H, et al. Nod2 is required for the regulation of commensal microbiota in the intestine. Proc Natl Acad Sci U S A. 2009;106:15813-8 pubmed publisher
    ..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. ..
  2. Nembrini C, Kisielow J, Shamshiev A, Tortola L, Coyle A, Kopf M, et al. The kinase activity of Rip2 determines its stability and consequently Nod1- and Nod2-mediated immune responses. J Biol Chem. 2009;284:19183-8 pubmed publisher
    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...
  3. Inohara N, del Peso L, Koseki T, Chen S, Nunez G. RICK, a novel protein kinase containing a caspase recruitment domain, interacts with CLARP and regulates CD95-mediated apoptosis. J Biol Chem. 1998;273:12296-300 pubmed
    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...
  4. Kobayashi K, Inohara N, Hernandez L, Galan J, Nunez G, Janeway C, et al. RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature. 2002;416:194-9 pubmed
    ..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...
  5. Shimada K, Chen S, Dempsey P, Sorrentino R, Alsabeh R, Slepenkin A, et al. The NOD/RIP2 pathway is essential for host defenses against Chlamydophila pneumoniae lung infection. PLoS Pathog. 2009;5:e1000379 pubmed publisher
    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...
  6. Kim Y, Park J, Shaw M, Franchi L, Inohara N, Nunez G. The cytosolic sensors Nod1 and Nod2 are critical for bacterial recognition and host defense after exposure to Toll-like receptor ligands. Immunity. 2008;28:246-57 pubmed publisher
    ..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...
  7. Anand P, Tait S, Lamkanfi M, Amer A, Nunez G, Pages G, et al. TLR2 and RIP2 pathways mediate autophagy of Listeria monocytogenes via extracellular signal-regulated kinase (ERK) activation. J Biol Chem. 2011;286:42981-91 pubmed publisher
    ..Here, we show that macrophages deficient in the TLR2 and NOD/RIP2 pathway display defective autophagy induction in response to L. monocytogenes...
  8. Magalhaes J, Lee J, Geddes K, Rubino S, Philpott D, Girardin S. Essential role of Rip2 in the modulation of innate and adaptive immunity triggered by Nod1 and Nod2 ligands. Eur J Immunol. 2011;41:1445-55 pubmed publisher
    ..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 ..
  9. Mariathasan S, Newton K, Monack D, Vucic D, French D, Lee W, et al. Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature. 2004;430:213-8 pubmed
    ..The adaptors ASC, Ipaf and RIP2 have each been proposed to regulate caspase-1 (also called interleukin (IL)-1 converting enzyme), which is ..
  10. Stetson D, Medzhitov R. Recognition of cytosolic DNA activates an IRF3-dependent innate immune response. Immunity. 2006;24:93-103 pubmed
    ..These findings define an innate immune response to DNA linked to type I interferon production. ..

Detail Information

Publications82

  1. Petnicki Ocwieja T, Hrncir T, Liu Y, Biswas A, Hudcovic T, Tlaskalova Hogenova H, et al. Nod2 is required for the regulation of commensal microbiota in the intestine. Proc Natl Acad Sci U S A. 2009;106:15813-8 pubmed publisher
    ..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. ..
  2. Nembrini C, Kisielow J, Shamshiev A, Tortola L, Coyle A, Kopf M, et al. The kinase activity of Rip2 determines its stability and consequently Nod1- and Nod2-mediated immune responses. J Biol Chem. 2009;284:19183-8 pubmed publisher
    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...
  3. Inohara N, del Peso L, Koseki T, Chen S, Nunez G. RICK, a novel protein kinase containing a caspase recruitment domain, interacts with CLARP and regulates CD95-mediated apoptosis. J Biol Chem. 1998;273:12296-300 pubmed
    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...
  4. Kobayashi K, Inohara N, Hernandez L, Galan J, Nunez G, Janeway C, et al. RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature. 2002;416:194-9 pubmed
    ..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...
  5. Shimada K, Chen S, Dempsey P, Sorrentino R, Alsabeh R, Slepenkin A, et al. The NOD/RIP2 pathway is essential for host defenses against Chlamydophila pneumoniae lung infection. PLoS Pathog. 2009;5:e1000379 pubmed publisher
    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...
  6. Kim Y, Park J, Shaw M, Franchi L, Inohara N, Nunez G. The cytosolic sensors Nod1 and Nod2 are critical for bacterial recognition and host defense after exposure to Toll-like receptor ligands. Immunity. 2008;28:246-57 pubmed publisher
    ..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...
  7. Anand P, Tait S, Lamkanfi M, Amer A, Nunez G, Pages G, et al. TLR2 and RIP2 pathways mediate autophagy of Listeria monocytogenes via extracellular signal-regulated kinase (ERK) activation. J Biol Chem. 2011;286:42981-91 pubmed publisher
    ..Here, we show that macrophages deficient in the TLR2 and NOD/RIP2 pathway display defective autophagy induction in response to L. monocytogenes...
  8. Magalhaes J, Lee J, Geddes K, Rubino S, Philpott D, Girardin S. Essential role of Rip2 in the modulation of innate and adaptive immunity triggered by Nod1 and Nod2 ligands. Eur J Immunol. 2011;41:1445-55 pubmed publisher
    ..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 ..
  9. Mariathasan S, Newton K, Monack D, Vucic D, French D, Lee W, et al. Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature. 2004;430:213-8 pubmed
    ..The adaptors ASC, Ipaf and RIP2 have each been proposed to regulate caspase-1 (also called interleukin (IL)-1 converting enzyme), which is ..
  10. Stetson D, Medzhitov R. Recognition of cytosolic DNA activates an IRF3-dependent innate immune response. Immunity. 2006;24:93-103 pubmed
    ..These findings define an innate immune response to DNA linked to type I interferon production. ..
  11. Tigno Aranjuez J, Asara J, Abbott D. Inhibition of RIP2's tyrosine kinase activity limits NOD2-driven cytokine responses. Genes Dev. 2010;24:2666-77 pubmed publisher
    ..sarcoidosis susceptibility protein NOD2 (nucleotide oligomerization domain protein 2) binds to the protein kinase RIP2 (receptor-interacting protein 2) to coordinate NF-?B (nuclear factor ? B)-mediated cytokine responses...
  12. Chin A, Dempsey P, Bruhn K, Miller J, Xu Y, Cheng G. Involvement of receptor-interacting protein 2 in innate and adaptive immune responses. Nature. 2002;416:190-4 pubmed
    ..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...
  13. Abbott D, Wilkins A, Asara J, Cantley L. The Crohn's disease protein, NOD2, requires RIP2 in order to induce ubiquitinylation of a novel site on NEMO. Curr Biol. 2004;14:2217-27 pubmed
    ..We show the NOD2-dependent ubiquitinylation of NEMO is dependent on the scaffolding protein kinase RIP2. Crohn's disease-associated polymorphisms of NOD2 show a decreased ability to bind RIP2, and this decreased ability ..
  14. Frutuoso M, Hori J, Pereira M, Junior D, Sonego F, Kobayashi K, et al. The pattern recognition receptors Nod1 and Nod2 account for neutrophil recruitment to the lungs of mice infected with Legionella pneumophila. Microbes Infect. 2010;12:819-27 pubmed publisher
    ..By using mice deficient for Nod1, Nod2, and Rip2, we found that these receptors accounted for NE recruitment to the lungs of infected mice...
  15. Yang Y, Yin C, Pandey A, Abbott D, Sassetti C, Kelliher M. NOD2 pathway activation by MDP or Mycobacterium tuberculosis infection involves the stable polyubiquitination of Rip2. J Biol Chem. 2007;282:36223-9 pubmed
    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...
  16. Park J, Kim Y, McDonald C, Kanneganti T, Hasegawa M, Body Malapel M, et al. RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs. J Immunol. 2007;178:2380-6 pubmed
    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...
  17. McCully M, Fairhead T, Colmont C, Beasley F, Heinrichs D, Blake P, et al. Receptor-interacting protein-2 deficiency delays macrophage migration and increases intracellular infection during peritoneal dialysis-associated peritonitis. Am J Nephrol. 2008;28:879-89 pubmed publisher
    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 ..
  18. Park J, Kim Y, Shaw M, Kanneganti T, Fujimoto Y, Fukase K, et al. Nod1/RICK and TLR signaling regulate chemokine and antimicrobial innate immune responses in mesothelial cells. J Immunol. 2007;179:514-21 pubmed
    ..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 ..
  19. Shaw P, Barr M, Lukens J, McGargill M, Chi H, Mak T, et al. Signaling via the RIP2 adaptor protein in central nervous system-infiltrating dendritic cells promotes inflammation and autoimmunity. Immunity. 2011;34:75-84 pubmed publisher
    ..NOD1 and NOD2 and their common downstream adaptor molecule, receptor interacting protein 2 (RIP2; also known as RIPK2 and RICK)...
  20. Yeretssian G, Correa R, Doiron K, Fitzgerald P, Dillon C, Green D, et al. Non-apoptotic role of BID in inflammation and innate immunity. Nature. 2011;474:96-9 pubmed publisher
    ..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. ..
  21. Park J, Kim Y, Nunez G. RICK promotes inflammation and lethality after gram-negative bacterial infection in mice stimulated with lipopolysaccharide. Infect Immun. 2009;77:1569-78 pubmed publisher
    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-..
  22. Koh Y, Koo J, Biswas A, Kobayashi K. MyD88-dependent signaling contributes to host defense against ehrlichial infection. PLoS ONE. 2010;5:e11758 pubmed publisher
  23. Jacquet S, Nishino Y, Kumphune S, Sicard P, Clark J, Kobayashi K, et al. The role of RIP2 in p38 MAPK activation in the stressed heart. J Biol Chem. 2008;283:11964-71 pubmed publisher
    ..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...
  24. Hall H, Wilhelm M, Saibil S, Mak T, Flavell R, Ohashi P. RIP2 contributes to Nod signaling but is not essential for T cell proliferation, T helper differentiation or TLR responses. Eur J Immunol. 2008;38:64-72 pubmed
    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 (..
  25. Kanneganti T, Lamkanfi M, Kim Y, Chen G, Park J, Franchi L, et al. Pannexin-1-mediated recognition of bacterial molecules activates the cryopyrin inflammasome independent of Toll-like receptor signaling. Immunity. 2007;26:433-43 pubmed
  26. Muto A, Ruland J, McAllister Lucas L, Lucas P, Yamaoka S, Chen F, et al. Protein kinase C-associated kinase (PKK) mediates Bcl10-independent NF-kappa B activation induced by phorbol ester. J Biol Chem. 2002;277:31871-6 pubmed
    ..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...
  27. Kim D, Kim Y, Seo S, Kim D, Kamada N, Prescott D, et al. Nod2-mediated recognition of the microbiota is critical for mucosal adjuvant activity of cholera toxin. Nat Med. 2016;22:524-30 pubmed publisher
    ..These results show a role for the microbiota and the intracellular receptor Nod2 in promoting the mucosal adjuvant activity of CT. ..
  28. Severa M, Islam S, Waggoner S, Jiang Z, Kim N, Ryan G, et al. The transcriptional repressor BLIMP1 curbs host defenses by suppressing expression of the chemokine CCL8. J Immunol. 2014;192:2291-304 pubmed publisher
    ..Finally, CCL8-mediated enhanced clearance of L. monocytogenes was dependent on ?/? T cells. Collectively, these data reveal an important role for BLIMP1 in modulating host defenses by suppressing expression of the chemokine CCL8. ..
  29. Zhang W, Wang X, Narayanan M, Zhang Y, Huo C, Reed J, et al. Fundamental role of the Rip2/caspase-1 pathway in hypoxia and ischemia-induced neuronal cell death. Proc Natl Acad Sci U S A. 2003;100:16012-7 pubmed
    ..Furthermore, we demonstrate that Rip2/Cardiak/Rick is a stress-inducible upstream modulator of pro-caspase-1 apoptotic activation...
  30. Hasegawa M, Osaka T, Tawaratsumida K, Yamazaki T, Tada H, Chen G, et al. Transitions in oral and intestinal microflora composition and innate immune receptor-dependent stimulation during mouse development. Infect Immun. 2010;78:639-50 pubmed publisher
    ..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...
  31. Meinzer U, Barreau F, Esmiol Welterlin S, Jung C, Villard C, Léger T, et al. Yersinia pseudotuberculosis effector YopJ subverts the Nod2/RICK/TAK1 pathway and activates caspase-1 to induce intestinal barrier dysfunction. Cell Host Microbe. 2012;11:337-51 pubmed publisher
    ..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...
  32. Hollenbach E, Neumann M, Vieth M, Roessner A, Malfertheiner P, Naumann M. Inhibition of p38 MAP kinase- and RICK/NF-kappaB-signaling suppresses inflammatory bowel disease. FASEB J. 2004;18:1550-2 pubmed
    ..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...
  33. Nachbur U, Vince J, O Reilly L, Strasser A, Silke J. Is BID required for NOD signalling?. Nature. 2012;488:E4-6; discussion E6-8 pubmed publisher
  34. Dufner A, Pownall S, Mak T. Caspase recruitment domain protein 6 is a microtubule-interacting protein that positively modulates NF-kappaB activation. Proc Natl Acad Sci U S A. 2006;103:988-93 pubmed
    ..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...
  35. Zhao C, Ma X, Guo H, Li P, Liu H. RIP2 deficiency attenuates cardiac hypertrophy, inflammation and fibrosis in pressure overload induced mice. Biochem Biophys Res Commun. 2017;493:1151-1158 pubmed publisher
    ..Here, we reported that receptor-interacting serine/threonine-protein kinase 2 (RIP2), promoting pro-inflammatory gene expression, enhanced the pathological cardiac hypertrophy in animals...
  36. Geddes K, Rubino S, Streutker C, Cho J, Magalhaes J, Le Bourhis L, et al. Nod1 and Nod2 regulation of inflammation in the Salmonella colitis model. Infect Immun. 2010;78:5107-15 pubmed publisher
    ..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 ..
  37. Zach S, Felk S, Gillardon F. Signal transduction protein array analysis links LRRK2 to Ste20 kinases and PKC zeta that modulate neuronal plasticity. PLoS ONE. 2010;5:e13191 pubmed publisher
    ..Our data suggest that these kinases may also be involved in synaptic dysfunction and neurite fragmentation in transgenic mice and in human PD patients carrying toxic gain-of-function LRRK2 mutations. ..
  38. Hsu L, Ali S, McGillivray S, Tseng P, Mariathasan S, Humke E, et al. A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide. Proc Natl Acad Sci U S A. 2008;105:7803-8 pubmed publisher
    ..Thus, NOD2 plays a key role in the B. anthracis-induced inflammatory response by being a critical mediator of IL-1beta secretion. ..
  39. Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science. 2011;331:337-41 pubmed publisher
  40. Zhang H, Chin A. Role of Rip2 in development of tumor-infiltrating MDSCs and bladder cancer metastasis. PLoS ONE. 2014;9:e94793 pubmed publisher
    ..In this study, we examined the downstream serine/threonine and tyrosine kinase Rip2 in a murine model of bladder cancer...
  41. Lu C, Wang A, Dorsch M, Tian J, Nagashima K, Coyle A, et al. Participation of Rip2 in lipopolysaccharide signaling is independent of its kinase activity. J Biol Chem. 2005;280:16278-83 pubmed
    Rip2 (Rick, Cardiak, CCK2, and CARD3) is a serine/threonine kinase containing a caspase recruitment domain (CARD) at the C terminus...
  42. Jeong Y, Kim C, Kim J, Oh S, Lee K, Park J, et al. RIP2/RICK-dependent cytokine production upon Yersinia enterocolitica infection in macrophages with TLR4 deficiency. Scand J Immunol. 2013;78:401-7 pubmed publisher
    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-?B and mitogen-activated ..
  43. Sharma P, Mackey A, Dejene E, Ramadan J, Langefeld C, Palmer N, et al. An Islet-Targeted Genome-Wide Association Scan Identifies Novel Genes Implicated in Cytokine-Mediated Islet Stress in Type 2 Diabetes. Endocrinology. 2015;156:3147-56 pubmed publisher
    ..3), F13a1 (6p25.3), Klhl6 (3q27.1), Nid1 (1q42.3), Pamr1 (11p13), Ripk2 (8q21.3), and Steap4 (7q21.12)...
  44. Fairhead T, Lian D, McCully M, Garcia B, Zhong R, Madrenas J. RIP2 is required for NOD signaling but not for Th1 cell differentiation and cellular allograft rejection. Am J Transplant. 2008;8:1143-50 pubmed publisher
    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-..
  45. Marchiando A, Ramanan D, Ding Y, Gómez L, Hubbard Lucey V, Maurer K, et al. A deficiency in the autophagy gene Atg16L1 enhances resistance to enteric bacterial infection. Cell Host Microbe. 2013;14:216-24 pubmed publisher
    ..These results reveal an immunosuppressive function of Atg16L1 and suggest that gene variants affecting the autophagy pathway may have been evolutionarily maintained to protect against certain life-threatening infections. ..
  46. Burrows M, Volchkov P, Kobayashi K, Chervonsky A. Microbiota regulates type 1 diabetes through Toll-like receptors. Proc Natl Acad Sci U S A. 2015;112:9973-7 pubmed publisher
    ..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. ..
  47. Corradi A, Croci L, Stayton C, Gulisano M, Boncinelli E, Consalez G. cDNA sequence, map, and expression of the murine homolog of GTBP, a DNA mismatch repair gene. Genomics. 1996;36:288-95 pubmed
    ..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. ..
  48. Balamayooran T, Batra S, Balamayooran G, Cai S, Kobayashi K, Flavell R, et al. Receptor-interacting protein 2 controls pulmonary host defense to Escherichia coli infection via the regulation of interleukin-17A. Infect Immun. 2011;79:4588-99 pubmed publisher
    ..coli infection model using mice deficient in the gene coding for the NLR adaptor, receptor-interacting protein 2 (RIP2). RIP2(-/-) mice with E...
  49. Porto Neto L, Jonsson N, Ingham A, Bunch R, Harrison B, Barendse W. The RIPK2 gene: a positional candidate for tick burden supported by genetic associations in cattle and immunological response of knockout mouse. Immunogenetics. 2012;64:379-88 pubmed publisher
    ..on BTA14 at ~72 Mb distal to the centromere, near the gene receptor-interacting serine-threonine kinase 2 (RIPK2)...
  50. Wang X, Deng S, Jiang D, Zhang R, Zhang S, Zhong J, et al. CARD3 deficiency exacerbates diet-induced obesity, hepatosteatosis, and insulin resistance in male mice. Endocrinology. 2013;154:685-97 pubmed publisher
    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...
  51. Sicard P, Jacquet S, Kobayashi K, Flavell R, Marber M. Pharmacological postconditioning effect of muramyl dipeptide is mediated through RIP2 and TAK1. Cardiovasc Res. 2009;83:277-84 pubmed publisher
    ..Receptor activation leads to intracellular signals through receptor interacting protein-2 (RIP2) and tumour growth factor-beta-activated kinase-1 (TAK1)...
  52. O Connell R, Vaidya S, Perry A, Saha S, Dempsey P, Cheng G. 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. J Immunol. 2005;174:1602-7 pubmed
    ..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. ..
  53. Brandl K, Plitas G, Schnabl B, Dematteo R, Pamer E. MyD88-mediated signals induce the bactericidal lectin RegIII gamma and protect mice against intestinal Listeria monocytogenes infection. J Exp Med. 2007;204:1891-900 pubmed
    ..Our findings support a model of MyD88-mediated epithelial conditioning that protects the intestinal mucosa against bacterial invasion by inducing RegIII gamma. ..
  54. Hruz P, Eckmann L. Caspase recruitment domain-containing sensors and adaptors in intestinal innate immunity. Curr Opin Gastroenterol. 2008;24:108-14 pubmed publisher
    ..the sensors interact through CARD domains with downstream CARD-containing adaptors including CARD9, RIP2 (CARD3) and ASC (CARD5)...
  55. Ermann J, Staton T, Glickman J, de Waal Malefyt R, Glimcher L. Nod/Ripk2 signaling in dendritic cells activates IL-17A-secreting innate lymphoid cells and drives colitis in T-bet-/-.Rag2-/- (TRUC) mice. Proc Natl Acad Sci U S A. 2014;111:E2559-66 pubmed publisher
    ..by nucleotide-binding oligomerization domain containing (Nod)/receptor-interacting serine-threonine kinase 2 (Ripk2) signals in DCs...
  56. Abbott D, Yang Y, Hutti J, Madhavarapu S, Kelliher M, Cantley L. Coordinated regulation of Toll-like receptor and NOD2 signaling by K63-linked polyubiquitin chains. Mol Cell Biol. 2007;27:6012-25 pubmed
    ..We further show that TRAF6 and NOD2/RIP2 share the same biochemical machinery (transforming growth factor beta-activated kinase 1 [TAK1]/TAB/Ubc13) to ..
  57. Ehlers S, Mueck T, Adams S, Landuzzi L, Lollini P, Munz B. RIP2 regulates growth and differentiation of normal myoblasts and of rhabdomyosarcoma cells. Eur J Cell Biol. 2008;87:163-72 pubmed
    b>RIP2 is an important regulator of myoblast proliferation and differentiation...
  58. Archer K, Ader F, Kobayashi K, Flavell R, Roy C. Cooperation between multiple microbial pattern recognition systems is important for host protection against the intracellular pathogen Legionella pneumophila. Infect Immun. 2010;78:2477-87 pubmed publisher
    ..b>Rip2 and Naip5/NLRC4 signaling was found to contribute to the innate immune response generated against L...
  59. Jeong M, Park D, Kim M, Park J, Kim D, Jeon Y, et al. Saengmaeksan inhibits inflammatory mediators by suppressing RIP-2/caspase-1 activation. Immunopharmacol Immunotoxicol. 2013;35:241-50 pubmed publisher
    ..Our results provide novel insights into the pharmacological actions of SMS, a molecule that can potentially be exploited in the treatment of inflammatory diseases. ..
  60. Ali S, Timmer A, Bilgrami S, Park E, Eckmann L, Nizet V, et al. Anthrax toxin induces macrophage death by p38 MAPK inhibition but leads to inflammasome activation via ATP leakage. Immunity. 2011;35:34-44 pubmed publisher
    ..Prevention of cell death or ATP release through constitutive p38 or AKT activation interfered with inflammasome activation and IL-1? production, thereby compromising antimicrobial immunity...
  61. Yan R, Liu Z. LRRK2 enhances Nod1/2-mediated inflammatory cytokine production by promoting Rip2 phosphorylation. Protein Cell. 2017;8:55-66 pubmed publisher
    ..Nod1/2-Rip2 signaling, which is essential for initiating the innate immune response to bacterial infection and ER stress, is ..
  62. Watanabe T, Asano N, Meng G, Yamashita K, Arai Y, Sakurai T, et al. NOD2 downregulates colonic inflammation by IRF4-mediated inhibition of K63-linked polyubiquitination of RICK and TRAF6. Mucosal Immunol. 2014;7:1312-25 pubmed publisher
    ..regulatory factor 4 (IRF4) expression and binding to tumor necrosis factor receptor associated factor 6 (TRAF6) and RICK (receptor interacting serine-threonine kinase)...
  63. Zhang Y, Cheng J, Zhang J, Wu X, Chen F, Ren X, et al. Proteasome inhibitor PS-341 limits macrophage necroptosis by promoting cIAPs-mediated inhibition of RIP1 and RIP3 activation. Biochem Biophys Res Commun. 2016;477:761-767 pubmed publisher
    ..Overall, our study has identified a new role of PS-341 in the cell death of BMDMs and provided a novel insight into the atherosclerotic inflammation caused by proteasome-mediated macrophage necroptosis. ..
  64. Shimada K, Crother T, Karlin J, Chen S, Chiba N, Ramanujan V, et al. Caspase-1 dependent IL-1? secretion is critical for host defense in a mouse model of Chlamydia pneumoniae lung infection. PLoS ONE. 2011;6:e21477 pubmed publisher
    ..Interestingly, Caspase-1 activation during CP infection occurs with mitochondrial dysfunction indicating a possible mechanism involving the mitochondria for CP-induced inflammasome activation...
  65. Sonego F, Castanheira F, Czaikoski P, Kanashiro A, Souto F, França R, et al. MyD88-, but not Nod1- and/or Nod2-deficient mice, show increased susceptibility to polymicrobial sepsis due to impaired local inflammatory response. PLoS ONE. 2014;9:e103734 pubmed publisher
    ..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...
  66. HUMPHRIES F, Yang S, Wang B, Moynagh P. RIP kinases: key decision makers in cell death and innate immunity. Cell Death Differ. 2015;22:225-36 pubmed publisher
    ..The function of RIP2, with particular emphasis on its role in NOD signalling, is also explored...
  67. Nachbur U, Stafford C, Bankovacki A, Zhan Y, Lindqvist L, Fiil B, et al. A RIPK2 inhibitor delays NOD signalling events yet prevents inflammatory cytokine production. Nat Commun. 2015;6:6442 pubmed publisher
    ..Receptor interacting protein kinase 2 (RIPK2) is critical for NOD-mediated NF-κB activation and cytokine production...
  68. Wex K, Schmid U, Just S, Wang X, Wurm R, Naumann M, et al. Receptor-Interacting Protein Kinase-2 Inhibition by CYLD Impairs Antibacterial Immune Responses in Macrophages. Front Immunol. 2015;6:650 pubmed publisher
    ..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-κ..
  69. Andersson L, Scharin Täng M, Lundqvist A, Lindbom M, Mardani I, Fogelstrand P, et al. Rip2 modifies VEGF-induced signalling and vascular permeability in myocardial ischaemia. Cardiovasc Res. 2015;107:478-86 pubmed publisher
    ..In this study, we investigated the role of receptor-interacting protein 2 (Rip2) in VEGF signalling and myocardial ischaemia/reperfusion injury...
  70. Damgaard R, Nachbur U, Yabal M, Wong W, Fiil B, Kastirr M, et al. The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in inflammation and innate immunity. Mol Cell. 2012;46:746-58 pubmed publisher
    ..We find that XIAP ubiquitylates RIPK2 and recruits the linear ubiquitin chain assembly complex (LUBAC) to NOD2...
  71. Vieira S, Cunha T, França R, Pinto L, Talbot J, Turato W, et al. Joint NOD2/RIPK2 signaling regulates IL-17 axis and contributes to the development of experimental arthritis. J Immunol. 2012;188:5116-22 pubmed publisher
    ..was generated in wild-type, NOD1(-/-), NOD2(-/-), or receptor-interacting serine-threonine kinase 2(-/-) (RIPK2(-/-)) immunized mice challenged intra-articularly with methylated BSA...
  72. Cassidy S, Hagar J, Kanneganti T, Franchi L, Nunez G, O Riordan M. Membrane damage during Listeria monocytogenes infection triggers a caspase-7 dependent cytoprotective response. PLoS Pathog. 2012;8:e1002628 pubmed publisher
    ..not require caspase-1 or key adaptors of the primary pathways of innate immune signaling in this infection, ASC, RIP2 and MyD88...
  73. Koch M, Mollenkopf H, Klemm U, Meyer T. Induction of microRNA-155 is TLR- and type IV secretion system-dependent in macrophages and inhibits DNA-damage induced apoptosis. Proc Natl Acad Sci U S A. 2012;109:E1153-62 pubmed publisher
    ..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. ..
  74. Prakhar P, Holla S, Ghorpade D, Gilleron M, Puzo G, Udupa V, et al. 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. J Biol Chem. 2015;290:26576-86 pubmed publisher
    ..microRNA expression profiling identified Ac2PIM-responsive miR-150 and miR-143 to target NOD2 signaling adaptors, RIP2 and TAK1, respectively...
  75. Skeldon A, Morizot A, Douglas T, Santoro N, Kursawe R, Kozlitina J, et al. Caspase-12, but Not Caspase-11, Inhibits Obesity and Insulin Resistance. J Immunol. 2016;196:437-47 pubmed publisher
  76. Nembrini C, Reissmann R, Kopf M, Marsland B. Effective T-cell immune responses in the absence of the serine/threonine kinase RIP2. Microbes Infect. 2008;10:522-30 pubmed publisher
    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...
  77. Kim B, Kang T, Jin S, Kim S, Lee S, Chae G. Tissue-specific down-regulation of RIPK 2 in Mycobacterium leprae-infected nu/nu mice. Mediators Inflamm. 2004;13:51-2 pubmed
    ..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. ..
  78. Jeong Y, Kang M, Lee S, Kim C, Kim J, Kim T, et al. Nod2 and Rip2 contribute to innate immune responses in mouse neutrophils. Immunology. 2014;143:269-76 pubmed publisher
    ..Increased production of cytokines and chemokines with MDP was abolished in Nod2- and Rip2-deficient neutrophils...
  79. Sukumaran B, Ogura Y, Pedra J, Kobayashi K, Flavell R, Fikrig E. Receptor interacting protein-2 contributes to host defense against Anaplasma phagocytophilum infection. FEMS Immunol Med Microbiol. 2012;66:211-9 pubmed publisher
    ..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...