Gene Symbol: Map3k14
Description: mitogen-activated protein kinase kinase kinase 14
Alias: Nik, aly, mitogen-activated protein kinase kinase kinase 14, NF kappa B-inducing kinase, NF-kappa-beta-inducing kinase, Nfkb inducing kinase, alymphoplasia, serine/threonine-protein kinase NIK
Species: mouse
Products:     Map3k14

Top Publications

  1. Lakkis F, Arakelov A, Konieczny B, Inoue Y. Immunologic 'ignorance' of vascularized organ transplants in the absence of secondary lymphoid tissue. Nat Med. 2000;6:686-8 pubmed
    ..Moreover, we demonstrate that the permanent acceptance of these grafts is not due to tolerance but is because of immunologic 'ignorance'. ..
  2. Xiao G, Harhaj E, Sun S. NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100. Mol Cell. 2001;7:401-9 pubmed
    ..Further, a natural mutation of the gene encoding NIK in alymphoplasia (aly) mice cripples the function of NIK in p100 processing, causing a severe defect in p52 production...
  3. Ishimaru N, Kishimoto H, Hayashi Y, Sprent J. Regulation of naive T cell function by the NF-kappaB2 pathway. Nat Immunol. 2006;7:763-72 pubmed
    ..Biochemical studies indicated involvement of a cell-intrinsic mechanism in which NF-kappaB2 (p100) limits nuclear translocation of NF-kappaB1-RelA and thereby functions as a regulatory 'brake' for the activation of naive T cells. ..
  4. Vallabhapurapu S, Matsuzawa A, Zhang W, Tseng P, Keats J, Wang H, et al. Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-kappaB signaling. Nat Immunol. 2008;9:1364-70 pubmed publisher
    ..alternative nuclear factor-kappaB (NF-kappaB) signaling in resting cells by targeting NF-kappaB-inducing kinase (NIK) for ubiquitin-dependent degradation, thus preventing processing of the NF-kappaB2 precursor protein p100 to ..
  5. Yin L, Wu L, Wesche H, Arthur C, White J, Goeddel D, et al. Defective lymphotoxin-beta receptor-induced NF-kappaB transcriptional activity in NIK-deficient mice. Science. 2001;291:2162-5 pubmed
    The role of NF-kappaB-inducing kinase (NIK) in cytokine signaling remains controversial. To identify the physiologic functions of NIK, we disrupted the NIK locus by gene targeting...
  6. Hamada H, Hiroi T, Nishiyama Y, Takahashi H, Masunaga Y, Hachimura S, et al. Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine. J Immunol. 2002;168:57-64 pubmed
    ..Neither ILF nor PP are detectable in lymphotoxin alpha(-/-) and aly/aly mice that retain well-developed cryptopatches (CP) and thymus-independent subsets of intraepithelial T cells, ..
  7. Greter M, Hofmann J, Becher B. Neo-lymphoid aggregates in the adult liver can initiate potent cell-mediated immunity. PLoS Biol. 2009;7:e1000109 pubmed publisher
    ..These structures are insufficient to support antibody affinity maturation and class switching, but provide a novel surrogate environment for the initiation of CMI. ..
  8. Karrer U, Althage A, Odermatt B, Roberts C, Korsmeyer S, Miyawaki S, et al. On the key role of secondary lymphoid organs in antiviral immune responses studied in alymphoplastic (aly/aly) and spleenless (Hox11(-)/-) mutant mice. J Exp Med. 1997;185:2157-70 pubmed
    ..homeobox gene 11 knockout mice (Hox11(-/-)) lacking the spleen, and in homozygous alymphoplastic mutant mice (aly/aly) possessing a structurally altered spleen but lacking lymph nodes and Peyer's patches...
  9. Suzuki K, Meek B, Doi Y, Honjo T, Fagarasan S. Two distinctive pathways for recruitment of naive and primed IgM+ B cells to the gut lamina propria. Proc Natl Acad Sci U S A. 2005;102:2482-6 pubmed
    ..Transfer experiments to reconstitute IgM+ B cells and IgA plasma cells in LP of aly/aly mice, which are defective in all organized follicular structures because of an NF-kappaB-inducing kinase (NIK) ..

More Information


  1. Matsumoto M, Iwamasa K, Rennert P, Yamada T, Suzuki R, Matsushima A, et al. Involvement of distinct cellular compartments in the abnormal lymphoid organogenesis in lymphotoxin-alpha-deficient mice and alymphoplasia (aly) mice defined by the chimeric analysis. J Immunol. 1999;163:1584-91 pubmed
    Both lymphotoxin-alpha (LTalpha)-deficient mice and alymphoplasia (aly) mice, a natural mutant strain, manifest a quite similar phenotype: lack of lymph nodes (LN) and Peyer's patches (PP), with disturbed spleen architecture...
  2. Park G, Wang X, Hu N, Pedchenko T, Blackwell T, Christman J. NIK is involved in nucleosomal regulation by enhancing histone H3 phosphorylation by IKKalpha. J Biol Chem. 2006;281:18684-90 pubmed
    The exact physiological role of NF-kappaB-inducing kinase (NIK) in the NF-kappaB activation pathway has not been defined, although it is an upstream kinase of IKKalpha...
  3. Karrer U, Althage A, Odermatt B, Hengartner H, Zinkernagel R. Immunodeficiency of alymphoplasia mice (aly/aly) in vivo: structural defect of secondary lymphoid organs and functional B cell defect. Eur J Immunol. 2000;30:2799-807 pubmed
    b>Alymphoplasia mice (aly/aly) have been shown to be deficient for a nuclear factor-kappaB-inducing kinase involved in signal transduction of lymphotoxin beta receptor (LT-betaR) and of CD40, resulting in structural defects of secondary ..
  4. Fukuyama S, Hiroi T, Yokota Y, Rennert P, Yanagita M, Kinoshita N, et al. Initiation of NALT organogenesis is independent of the IL-7R, LTbetaR, and NIK signaling pathways but requires the Id2 gene and CD3(-)CD4(+)CD45(+) cells. Immunity. 2002;17:31-40 pubmed
    ..PP) and peripheral lymph nodes (PLN), a cytokine cascade which consists of IL-7R, LTalpha1beta2/LTbetaR, and NIK. However, the subsequent organization of NALT seems to be controlled by these cytokine signaling cascades since the ..
  5. Tsuji M, Suzuki K, Kitamura H, Maruya M, Kinoshita K, Ivanov I, et al. Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut. Immunity. 2008;29:261-71 pubmed publisher
    ..These findings provide insight into the crosstalk between bacteria, ROR gamma t(+)LTi cells, SCs, DCs, and B cells required for ILF formation and establish a critical role of ILFs in T cell-independent IgA synthesis in gut. ..
  6. Shinkura R, Kitada K, Matsuda F, Tashiro K, Ikuta K, Suzuki M, et al. Alymphoplasia is caused by a point mutation in the mouse gene encoding Nf-kappa b-inducing kinase. Nat Genet. 1999;22:74-7 pubmed
    The alymphoplasia (aly) mutation of mouse is autosomal recessive and characterized by the systemic absence of lymph nodes (LN) and Peyer's patches (PP) and disorganized splenic and thymic structures with immunodeficiency...
  7. Bhattacharyya S, Borthakur A, Dudeja P, Tobacman J. Lipopolysaccharide-induced activation of NF-?B non-canonical pathway requires BCL10 serine 138 and NIK phosphorylations. Exp Cell Res. 2010;316:3317-27 pubmed publisher
    ..pathway of NF-?B activation, including nuclear RelB and p52 and phospho- and total NF-?B inducing kinase (NIK)...
  8. Kuramoto T, Mashimo T, Koike R, Miyawaki S, Yamada J, Miyasaka M, et al. The alymphoplasia (aly) mutation co-segregates with the intercellular adhesion molecule-2 (lcam-2) on mouse chromosome 11. Int Immunol. 1994;6:991-4 pubmed
    A new spontaneous autosomal recessive mutation alymphoplasia (aly), which causes a systemic defect of lymph nodes and Peyer's patches, was mapped on mouse chromosome 11 by linkage analysis using (ALY x MSM)F1 x ALY backcross progeny (155 ..
  9. Akiyama T, Shimo Y, Yanai H, Qin J, Ohshima D, Maruyama Y, et al. The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance. Immunity. 2008;29:423-37 pubmed publisher
    ..vitro induced mTEC development in a tumor necrosis factor-associated factor 6 (TRAF6)-, NF-kappaB inducing kinase (NIK)-, and IkappaB kinase beta (IKKbeta)-dependent manner...
  10. Sánchez Valdepeñas C, Martin A, Ramakrishnan P, Wallach D, Fresno M. NF-kappaB-inducing kinase is involved in the activation of the CD28 responsive element through phosphorylation of c-Rel and regulation of its transactivating activity. J Immunol. 2006;176:4666-74 pubmed
    ..Splenic T cells from aly/aly mice (that have a defective NIK protein) have a severe impairment in IL-2 and GM-CSF but not TNF secretion in ..
  11. Maruyama T, Fukushima H, Nakao K, Shin M, Yasuda H, Weih F, et al. Processing of the NF-kappa B2 precursor p100 to p52 is critical for RANKL-induced osteoclast differentiation. J Bone Miner Res. 2010;25:1058-67 pubmed publisher
    ..To address this issue, we analyzed alymphoplasia (aly/aly) mice in which the processing of p100 to p52 does not occur owing to an inactive form of NF-kappaB-..
  12. Aya K, Alhawagri M, Hagen Stapleton A, Kitaura H, Kanagawa O, Novack D. NF-(kappa)B-inducing kinase controls lymphocyte and osteoclast activities in inflammatory arthritis. J Clin Invest. 2005;115:1848-54 pubmed
    NF-(kappa)B is an important component of both autoimmunity and bone destruction in RA. NF-(kappa)B-inducing kinase (NIK) is a key mediator of the alternative arm of the NF-(kappa)B pathway, which is characterized by the nuclear ..
  13. Zarnegar B, Yamazaki S, He J, Cheng G. Control of canonical NF-kappaB activation through the NIK-IKK complex pathway. Proc Natl Acad Sci U S A. 2008;105:3503-8 pubmed publisher
    ..of the canonical NF-kappaB pathway in TRAF3-deficient cells results from accumulation of NF-kappaB-inducing kinase (NIK), the essential kinase mediating noncanonical NF-kappaB activation...
  14. Yilmaz Z, Weih D, Sivakumar V, Weih F. RelB is required for Peyer's patch development: differential regulation of p52-RelB by lymphotoxin and TNF. EMBO J. 2003;22:121-30 pubmed
    ..requires the degradation of the inhibitory p52 precursor, p100, which is mediated by the NF-kappaB-inducing kinase (NIK) and the IkappaB kinase (IKK) complex subunit IKKalpha, but not IKKbeta or IKKgamma...
  15. Matsushima A, Kaisho T, Rennert P, Nakano H, Kurosawa K, Uchida D, et al. Essential role of nuclear factor (NF)-kappaB-inducing kinase and inhibitor of kappaB (IkappaB) kinase alpha in NF-kappaB activation through lymphotoxin beta receptor, but not through tumor necrosis factor receptor I. J Exp Med. 2001;193:631-6 pubmed
    Both nuclear factor (NF)-kappaB-inducing kinase (NIK) and inhibitor of kappaB (IkappaB) kinase (IKK) have been implicated as essential components for NF-kappaB activation in response to many external stimuli...
  16. Zarnegar B, Wang Y, Mahoney D, Dempsey P, Cheung H, He J, et al. Noncanonical NF-kappaB activation requires coordinated assembly of a regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the kinase NIK. Nat Immunol. 2008;9:1371-8 pubmed publisher
    Recent studies suggest that nuclear factor kappaB-inducing kinase (NIK) is suppressed through constitutive proteasome-mediated degradation regulated by TRAF2, TRAF3 and cIAP1 or cIAP2...
  17. Matsumoto M, Yamada T, Yoshinaga S, Boone T, Horan T, Fujita S, et al. Essential role of NF-kappa B-inducing kinase in T cell activation through the TCR/CD3 pathway. J Immunol. 2002;169:1151-8 pubmed
    ..NIK in T cell activation through TCR/CD3 and costimulation pathways, we have studied the function of T cells from aly mice, a strain with mutant NIK...
  18. Murray S, Polesso F, Rowe A, Basak S, Koguchi Y, Toren K, et al. NF-?B–inducing kinase plays an essential T cell–intrinsic role in graft-versus-host disease and lethal autoimmunity in mice. J Clin Invest. 2011;121:4775-86 pubmed publisher
    NF-?B–inducing kinase (NIK) is an essential upstream kinase in noncanonical NF-?B signaling. NIK-dependent NF-?B activation downstream of several TNF receptor family members mediates lymphoid organ development and B cell homeostasis...
  19. Kinoshita D, Hirota F, Kaisho T, Kasai M, Izumi K, Bando Y, et al. Essential role of IkappaB kinase alpha in thymic organogenesis required for the establishment of self-tolerance. J Immunol. 2006;176:3995-4002 pubmed
    ..Because a natural strain of mice with mutant NF-kappaB-inducing kinase (NIK) manifests autoimmunity as a result of disorganized thymic structure with abnormal expression of Rel proteins in ..
  20. Jin W, Zhou X, Yu J, Cheng X, Sun S. Regulation of Th17 cell differentiation and EAE induction by MAP3K NIK. Blood. 2009;113:6603-10 pubmed publisher
    ..We show here that NF-kappaB-inducing kinase (NIK), which is known to regulate B-cell maturation and lymphoid organogenesis, is important for the induction of Th17 ..
  21. Feuerer M, Beckhove P, Garbi N, Mahnke Y, Limmer A, Hommel M, et al. Bone marrow as a priming site for T-cell responses to blood-borne antigen. Nat Med. 2003;9:1151-7 pubmed
    ..These findings highlight the uniqueness of bone marrow as an organ important for hemato- and lymphopoiesis and for systemic T cell-mediated immunity. ..
  22. Miyawaki S, Nakamura Y, Suzuka H, Koba M, Yasumizu R, Ikehara S, et al. A new mutation, aly, that induces a generalized lack of lymph nodes accompanied by immunodeficiency in mice. Eur J Immunol. 1994;24:429-34 pubmed
    ..The name "alymphoplasia", with the gene symbol "aly", is proposed for this mutant...
  23. Tamura C, Nakazawa M, Kasahara M, Hotta C, Yoshinari M, Sato F, et al. Impaired function of dendritic cells in alymphoplasia (aly/aly) mice for expansion of CD25+CD4+ regulatory T cells. Autoimmunity. 2006;39:445-53 pubmed
    b>Alymphoplasia (aly/aly) mice are from a naturally occurring strain with a mutation in nuclear factor-kappa B inducing kinase (NIK)...
  24. de Leon Boenig G, Bowman K, Feng J, Crawford T, Everett C, Franke Y, et al. The crystal structure of the catalytic domain of the NF-?B inducing kinase reveals a narrow but flexible active site. Structure. 2012;20:1704-14 pubmed publisher
    The NF-?B inducing kinase (NIK) regulates the non-canonical NF-?B pathway downstream of important clinical targets including BAFF, RANKL, and LT?...
  25. Koike R, Watanabe T, Satoh H, Hee C, Kitada K, Kuramoto T, et al. Analysis of expression of lymphocyte homing-related adhesion molecules in ALY mice deficient in lymph nodes and Peyer's patches. Cell Immunol. 1997;180:62-9 pubmed
    The aly, alymphoplasia, is an autosomal recessive mutation in mice of an unknown etiology, which induces total aplasia of lymph nodes and Peyer's patches...
  26. Lu L, Gondek D, Scott Z, Noelle R. NF kappa B-inducing kinase deficiency results in the development of a subset of regulatory T cells, which shows a hyperproliferative activity upon glucocorticoid-induced TNF receptor family-related gene stimulation. J Immunol. 2005;175:1651-7 pubmed
    ..A recent study reports that NF-kappaB-inducing kinase (NIK) expression in thymic stroma is important for the normal production of T(reg) but not for its suppression capacity...
  27. Vaira S, Johnson T, Hirbe A, Alhawagri M, Anwisye I, Sammut B, et al. RelB is the NF-kappaB subunit downstream of NIK responsible for osteoclast differentiation. Proc Natl Acad Sci U S A. 2008;105:3897-902 pubmed publisher
    NF-kappaB inducing kinase (NIK) is required for osteoclastogenesis in response to pathologic stimuli, and its loss leads to functional blockade of both alternative and classical NF-kappaB caused by cytoplasmic retention by p100...
  28. Razani B, Zarnegar B, Ytterberg A, Shiba T, Dempsey P, Ware C, et al. Negative feedback in noncanonical NF-kappaB signaling modulates NIK stability through IKKalpha-mediated phosphorylation. Sci Signal. 2010;3:ra41 pubmed publisher
    ..control of noncanonical NF-kappaB signaling that attenuated the stabilization of NF-kappaB-inducing kinase (NIK), the central regulatory kinase of the noncanonical pathway, induced by B cell-activating factor receptor (BAFF-R) ..
  29. Sanjo H, Zajonc D, Braden R, Norris P, Ware C. Allosteric regulation of the ubiquitin:NIK and ubiquitin:TRAF3 E3 ligases by the lymphotoxin-beta receptor. J Biol Chem. 2010;285:17148-55 pubmed publisher
    ..activates the NF-kappaB2 transcription factors, p100 and RelB, by regulating the NF-kappaB-inducing kinase (NIK)...
  30. Sasaki Y, Calado D, Derudder E, Zhang B, Shimizu Y, Mackay F, et al. NIK overexpression amplifies, whereas ablation of its TRAF3-binding domain replaces BAFF:BAFF-R-mediated survival signals in B cells. Proc Natl Acad Sci U S A. 2008;105:10883-8 pubmed publisher
    ..Mutations leading to overexpression of NIK and deletion of the TRAF3 gene are implicated in human multiple myeloma...
  31. Kajiura F, Sun S, Nomura T, Izumi K, Ueno T, Bando Y, et al. NF-kappa B-inducing kinase establishes self-tolerance in a thymic stroma-dependent manner. J Immunol. 2004;172:2067-75 pubmed
    ..We used a mouse strain with mutant NF-kappaB-inducing kinase (NIK) to examine the mechanisms underlying the breakdown of self-tolerance...
  32. Sánchez Valdepeñas C, Casanova L, Colmenero I, Arriero M, González A, Lozano N, et al. Nuclear factor-kappaB inducing kinase is required for graft-versus-host disease. Haematologica. 2010;95:2111-8 pubmed publisher
    ..effect of nuclear factor-? B inducing kinase in a murine model of graft-versus-host disease using donor cells from aly/aly mice (deficient in nuclear factor-? B inducing kinase) and C57BL/6 mice (control)...
  33. Nanno M, Matsumoto S, Koike R, Miyasaka M, Kawaguchi M, Masuda T, et al. Development of intestinal intraepithelial T lymphocytes is independent of Peyer's patches and lymph nodes in aly mutant mice. J Immunol. 1994;153:2014-20 pubmed
    ..lack of lymph nodes (LNs) and Peyer's patches (PPs) accompanied by immunodeficiency in mice (gene symbol, aly)...
  34. Koike R, Nishimura T, Yasumizu R, Tanaka H, Hataba Y, Watanabe T, et al. The splenic marginal zone is absent in alymphoplastic aly mutant mice. Eur J Immunol. 1996;26:669-75 pubmed
    b>aly is a unique spontaneous autosomal recessive mutation in mice that causes a deficiency in the systemic lymph nodes (LN) and Peyer's patches (PP)...
  35. Shinkura R, Matsuda F, Sakiyama T, Tsubata T, Hiai H, Paumen M, et al. Defects of somatic hypermutation and class switching in alymphoplasia (aly) mutant mice. Int Immunol. 1996;8:1067-75 pubmed
    The alymphoplasia (aly) mutation of mice causes the systemic absence of lymph nodes, Peyer's patches and well-defined lymphoid follicles in the spleen...
  36. Konishi J, Iwabuchi K, Iwabuchi C, Ato M, Nagata J, Nakagawa K, et al. Thymic epithelial cells responsible for impaired generation of NK-T thymocytes in Alymphoplasia mutant mice. Cell Immunol. 2000;206:26-35 pubmed
    ..1+TCRalphabeta+ (NK-T) cell population is severely impaired in an alymphoplasia mutant (aly/aly) mouse strain and the defect resides in the thymic environment...
  37. Yamada T, Mitani T, Yorita K, Uchida D, Matsushima A, Iwamasa K, et al. Abnormal immune function of hemopoietic cells from alymphoplasia (aly) mice, a natural strain with mutant NF-kappa B-inducing kinase. J Immunol. 2000;165:804-12 pubmed
    b>Alymphoplasia (aly) mice, a natural strain with a mutant NF-kappa B-inducing kinase (NIK) gene, manifest a unique phenotype; they lack lymph nodes and Peyer's patches, have a disturbed spleen architecture, and exhibit defects in both Ab ..
  38. Garceau N, Kosaka Y, Masters S, Hambor J, Shinkura R, Honjo T, et al. Lineage-restricted function of nuclear factor kappaB-inducing kinase (NIK) in transducing signals via CD40. J Exp Med. 2000;191:381-6 pubmed
    ..Nuclear factor kappaB (NF-kappaB)-inducing kinase (NIK) has been implicated as a central transducing kinase in CD40-dependent activation...
  39. Cariappa A, Chase C, Liu H, Russell P, Pillai S. Naive recirculating B cells mature simultaneously in the spleen and bone marrow. Blood. 2007;109:2339-45 pubmed
    ..These data suggest that newly formed B cells mature into IgD(hi) B cells simultaneously in the spleen and the bone marrow and establish in a stringent manner that humoral immune responses can be initiated in situ in the bone marrow. ..
  40. Fusco A, Mazumder A, Wang V, Tao Z, Ware C, Ghosh G. The NF-κB subunit RelB controls p100 processing by competing with the kinases NIK and IKK1 for binding to p100. Sci Signal. 2016;9:ra96 pubmed publisher
    ..The kinases NF-κB-inducing kinase (NIK) and inhibitor of κB kinase 1 (IKK1; also known as IKKα) are activated during noncanonical signaling and play ..
  41. Blackburn J, Kawasaki K, Porntaveetus T, Kawasaki M, Otsuka Tanaka Y, Miake Y, et al. Excess NF-κB induces ectopic odontogenesis in embryonic incisor epithelium. J Dent Res. 2015;94:121-8 pubmed publisher
    ..Excess NF-κB activity thus induces an ectopic odontogenesis program that is usually suppressed under physiological conditions. ..
  42. Anderson B, Taylor P, McNiff J, Jain D, Demetris A, Panoskaltsis Mortari A, et al. Effects of donor T-cell trafficking and priming site on graft-versus-host disease induction by naive and memory phenotype CD4 T cells. Blood. 2008;111:5242-51 pubmed publisher
    ..Taken together, these data argue against the hypothesis that T(EM) fail to induce GVHD because of inefficient trafficking to LN and PP. ..
  43. Boutaffala L, Bertrand M, Remouchamps C, Seleznik G, Reisinger F, Janas M, et al. NIK promotes tissue destruction independently of the alternative NF-κB pathway through TNFR1/RIP1-induced apoptosis. Cell Death Differ. 2015;22:2020-33 pubmed publisher
    NF-κB-inducing kinase (NIK) is well-known for its role in promoting p100/NF-κB2 processing into p52, a process defined as the alternative, or non-canonical, NF-κB pathway...
  44. Qin J, Konno H, Ohshima D, Yanai H, Motegi H, Shimo Y, et al. Developmental stage-dependent collaboration between the TNF receptor-associated factor 6 and lymphotoxin pathways for B cell follicle organization in secondary lymphoid organs. J Immunol. 2007;179:6799-807 pubmed
    ..These data suggest that developmentally regulated activation of TRAF6 in FDCs is required for inducing CXCL13 expression to maintain B cell follicles. ..
  45. Nishikawa S, Nakane A. Host resistance against Listeria monocytogenes is reciprocal during the course of infection in alymphoplastic aly mutant mice. Cell Immunol. 1998;187:88-94 pubmed
    The aly is a unique spontaneous autosomal recessive mutation in mice that causes a systemic defect of lymph nodes and Peyer's patches. We investigated host resistance against Listeria monocytogenes infection in the mutant...
  46. Eshima K, Okabe M, Kajiura S, Noma H, Shinohara N, Iwabuchi K. Significant involvement of nuclear factor-?B-inducing kinase in proper differentiation of ?? and ?? T cells. Immunology. 2014;141:222-32 pubmed publisher
    ..This is exemplified in the spontaneous mutant mouse lacking functional NIK, alymphoplasia (aly), which is simultaneously immune-compromised and autoimmune-prone...
  47. Matsumoto M. Role of TNF ligand and receptor family in the lymphoid organogenesis defined by gene targeting. J Med Invest. 1999;46:141-50 pubmed
    ..the defective lymphoid organogenesis in LT alpha-deficient mice, together with a natural mutant strain, alymphoplasia (aly) mice, which manifest a quite similar phenotype to LT alpha-deficient mice, were investigated by ..
  48. Yan W, Nehrke K, Choi J, Barber D. The Nck-interacting kinase (NIK) phosphorylates the Na+-H+ exchanger NHE1 and regulates NHE1 activation by platelet-derived growth factor. J Biol Chem. 2001;276:31349-56 pubmed
    b>NIK, a recently identified Nck-interacting kinase, acts upstream of the MEK kinase MEKK1 to activate the c-Jun N-terminal kinase JNK. We now show that NIK binds to and divergently activates the plasma membrane Na(+)-H(+) exchanger NHE1...
  49. Hahn M, Macht A, Waisman A, Hövelmeyer N. NF-κB-inducing kinase is essential for B-cell maintenance in mice. Eur J Immunol. 2016;46:732-41 pubmed publisher
    NF-κB-inducing kinase (NIK) is a key mediator of the noncanonical NF-κB signaling pathway, which is critical for normal B-cell development and function...
  50. Ohmae T, Hirata Y, Maeda S, Shibata W, Yanai A, Ogura K, et al. Helicobacter pylori activates NF-kappaB via the alternative pathway in B lymphocytes. J Immunol. 2005;175:7162-9 pubmed
    ..The effects on chemokine production and antiapoptosis mediated by H. pylori-induced processing of NF-kappaB2/p100 to p52 may drive lymphocytes to acquire malignant potential. ..
  51. Zhang W, Tan W, Wu X, Poustovoitov M, Strasner A, Li W, et al. A NIK-IKK? module expands ErbB2-induced tumor-initiating cells by stimulating nuclear export of p27/Kip1. Cancer Cell. 2013;23:647-59 pubmed publisher
    ..Here, we show that IKK? and its activator, NF-?B-inducing kinase (NIK), support the expansion of tumor-initiating cells (TICs) that copurify with a CD24(med)CD49f(hi) population from ..
  52. Malle E, Zammit N, Walters S, Koay Y, Wu J, Tan B, et al. Nuclear factor κB-inducing kinase activation as a mechanism of pancreatic β cell failure in obesity. J Exp Med. 2015;212:1239-54 pubmed publisher
    ..Here, we demonstrate that pharmacological activation of the noncanonical NF-κB-inducing kinase (NIK) disrupts glucose homeostasis in zebrafish in vivo...
  53. Shen H, Sheng L, Xiong Y, Kim Y, Jiang L, Chen Z, et al. Thymic NF-κB-inducing kinase regulates CD4+ T cell-elicited liver injury and fibrosis in mice. J Hepatol. 2017;67:100-109 pubmed publisher
    ..Nuclear factor-κB-inducing kinase (NIK) is known to regulate immune tissue development, but its role in maintaining liver homeostasis remains unknown...
  54. Jin J, Xiao Y, Hu H, Zou Q, Li Y, Gao Y, et al. Proinflammatory TLR signalling is regulated by a TRAF2-dependent proteolysis mechanism in macrophages. Nat Commun. 2015;6:5930 pubmed publisher
    ..These findings demonstrate an unexpected anti-inflammatory function of TRAF2 and suggest a proteasome-dependent mechanism that limits the proinflammatory TLR signalling. ..
  55. Yang C, MCCOY K, Davis J, Schmidt Supprian M, Sasaki Y, Faccio R, et al. NIK stabilization in osteoclasts results in osteoporosis and enhanced inflammatory osteolysis. PLoS ONE. 2010;5:e15383 pubmed publisher
    ..NF-?B inducing kinase (NIK) controls activation of the alternative NF-?B pathway, a critical pathway for OC differentiation...
  56. Honke N, Shaabani N, Cadeddu G, Sorg U, Zhang D, Trilling M, et al. Enforced viral replication activates adaptive immunity and is essential for the control of a cytopathic virus. Nat Immunol. 2011;13:51-7 pubmed publisher
    ..In conclusion, we found that enforced viral replication in marginal zone macrophages was an immunological mechanism that ensured the production of sufficient antigen for effective activation of the adaptive immune response. ..
  57. Shinzawa M, Maruyama Y, Qin J, Akiyama N, Miyauchi M, Yanai H, et al. Splenic extramedullary hemopoiesis caused by a dysfunctional mutation in the NF-?B-inducing kinase gene. Biochem Biophys Res Commun. 2011;414:773-8 pubmed publisher
    ..b>Alymphoplasia (aly/aly) mice have a point mutation in the NIK gene that causes a defect in the activation of an NF-?B member ..
  58. De Trez C, Schneider K, Potter K, Droin N, Fulton J, Norris P, et al. The inhibitory HVEM-BTLA pathway counter regulates lymphotoxin receptor signaling to achieve homeostasis of dendritic cells. J Immunol. 2008;180:238-48 pubmed
    ..These results indicate the HVEM-BTLA pathway provides an inhibitory checkpoint for DC homeostasis in lymphoid tissue. Together, the LTbetaR and HVEM-BTLA pathways form an integrated signaling network regulating DC homeostasis. ..
  59. Gray C, McCorkell K, Chunduru S, McKinlay M, May M. Negative feedback regulation of NF-?B-inducing kinase is proteasome-dependent but does not require cellular inhibitors of apoptosis. Biochem Biophys Res Commun. 2014;450:341-6 pubmed publisher
    Non-canonical NF-?B signaling is controlled by the precise regulation of NF-?B inducing kinase (NIK) stability...
  60. Bhattacharyya S, Dudeja P, Tobacman J. Tumor necrosis factor alpha-induced inflammation is increased but apoptosis is inhibited by common food additive carrageenan. J Biol Chem. 2010;285:39511-22 pubmed publisher secretion of IL-8 occurred, attributable to synergistic effects on phosphorylated NF-?B-inducing kinase (NIK) in the non-canonical pathway...
  61. Chamoto K, Wakita D, Narita Y, Zhang Y, Noguchi D, Ohnishi H, et al. An essential role of antigen-presenting cell/T-helper type 1 cell-cell interactions in draining lymph node during complete eradication of class II-negative tumor tissue by T-helper type 1 cell therapy. Cancer Res. 2006;66:1809-17 pubmed
    ..Th1 cells or generation of tetramer+ CTL was not induced in MHC class II-deficient mice and LN-deficient Aly/Aly mice...
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