notch2 receptor


Summary: A notch receptor that plays an important role in CELL DIFFERENTIATION in a variety of cell types. It is the preferentially expressed notch receptor in mature B-LYMPHOCYTES.

Top Publications

  1. Gordon W, Roy M, Vardar Ulu D, Garfinkel M, Mansour M, Aster J, et al. Structure of the Notch1-negative regulatory region: implications for normal activation and pathogenic signaling in T-ALL. Blood. 2009;113:4381-90 pubmed publisher
    ..The Notch1 NRR structure should facilitate a search for antibodies or compounds that stabilize the autoinhibited conformation. ..
  2. Lee S, Kumano K, Nakazaki K, Sanada M, Matsumoto A, Yamamoto G, et al. Gain-of-function mutations and copy number increases of Notch2 in diffuse large B-cell lymphoma. Cancer Sci. 2009;100:920-6 pubmed
    ..These findings implicate Notch2 gain-of-function mutations in the pathogenesis of a subset of B-cell lymphomas, and suggest broader roles for Notch gene mutations in human cancers. ..
  3. Yoon S, Zhang X, Berner P, Blom B, Choi Y. Notch ligands expressed by follicular dendritic cells protect germinal center B cells from apoptosis. J Immunol. 2009;183:352-8 pubmed publisher
    ..Taken together, our data shows the important role of Notch signaling provided by FDC in the survival of GC-B cells in vitro...
  4. Dumortier A, Durham A, Di Piazza M, Vauclair S, Koch U, Ferrand G, et al. Atopic dermatitis-like disease and associated lethal myeloproliferative disorder arise from loss of Notch signaling in the murine skin. PLoS ONE. 2010;5:e9258 pubmed publisher
    ..Our data demonstrate a critical role for Notch in repressing TSLP production in keratinocytes, thereby maintaining integrity of the skin and the hematopoietic system. ..
  5. Sun S, Du R, Gao J, Ning X, Xie H, Lin X, et al. Expression and clinical significance of Notch receptors in human renal cell carcinoma. Pathology. 2009;41:335-41 pubmed publisher
    ..Our findings indicated that the expression of Notch receptors was deregulated and Notch signalling might play an important role in the progress of renal cell carcinoma. ..
  6. Fan X, Khaki L, Zhu T, Soules M, Talsma C, Gul N, et al. NOTCH pathway blockade depletes CD133-positive glioblastoma cells and inhibits growth of tumor neurospheres and xenografts. Stem Cells. 2010;28:5-16 pubmed publisher
    ..In summary, we demonstrate that NOTCH pathway blockade depletes stem-like cells in GBMs, suggesting that GSIs may be useful as chemotherapeutic reagents to target CSCs in malignant gliomas. ..
  7. Mikhailik A, Mazella J, Liang S, Tseng L. Notch ligand-dependent gene expression in human endometrial stromal cells. Biochem Biophys Res Commun. 2009;388:479-82 pubmed publisher
    ..This study provides evidence that Notch ligands control the Notch gene activities and may enhance development of human endometrium. ..
  8. Liu R, Li X, Tulpule A, Zhou Y, Scehnet J, Zhang S, et al. KSHV-induced notch components render endothelial and mural cell characteristics and cell survival. Blood. 2010;115:887-95 pubmed publisher
    ..Soluble Dll4 was also highly active in vivo against KS tumor xenograft. It inhibited tumor cell growth, induced tumor cell death, and reduced vessel perfusion. Soluble Dll4 is thus a candidate for clinical investigation. ..
  9. Sugimoto K, Maekawa Y, Kitamura A, Nishida J, Koyanagi A, Yagita H, et al. Notch2 signaling is required for potent antitumor immunity in vivo. J Immunol. 2010;184:4673-8 pubmed publisher
    ..These findings indicate that Notch2 signaling in CD8(+) T cells is required for generating potent antitumor CTLs, thus providing a crucial target for augmenting tumor immune responses. ..

More Information


  1. Sparks E, Huppert K, Brown M, Washington M, Huppert S. Notch signaling regulates formation of the three-dimensional architecture of intrahepatic bile ducts in mice. Hepatology. 2010;51:1391-400 pubmed publisher
  2. Li Y, Guessous F, Zhang Y, Dipierro C, Kefas B, Johnson E, et al. MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer Res. 2009;69:7569-76 pubmed publisher
    ..They show that miR-34a suppresses brain tumor growth by targeting c-Met and Notch. The results also suggest that miR-34a could serve as a potential therapeutic agent for brain tumors. ..
  3. Chu D, Zheng J, Wang W, Zhao Q, Li Y, Li J, et al. Notch2 expression is decreased in colorectal cancer and related to tumor differentiation status. Ann Surg Oncol. 2009;16:3259-66 pubmed publisher
    ..A clear increase expression of Notch2 was observed. Notch2 expression correlated closely with CRC and may play a role in tumor inhibition in colon carcinogenesis. ..
  4. Mullendore M, Koorstra J, Li Y, Offerhaus G, Fan X, Henderson C, et al. Ligand-dependent Notch signaling is involved in tumor initiation and tumor maintenance in pancreatic cancer. Clin Cancer Res. 2009;15:2291-301 pubmed publisher
    ..Our studies confirm that Notch activation is almost always ligand dependent in pancreatic cancer, and inhibition of Notch signaling is a promising therapeutic strategy in this malignancy. ..
  5. Varadkar P, Kraman M, McCright B. Generation of mice that conditionally express the activation domain of Notch2. Genesis. 2009;47:573-8 pubmed publisher
    ..In contrast, a cell nonautonomous mesenchymal expansion was observed in semilunar valves. This new conditionally expressed allele of Notch2 can be used in studies by investigators interested in the effects of Notch2 activation in vivo. ..
  6. Xu P, Yu S, Jiang R, Kang C, Wang G, Jiang H, et al. Differential expression of Notch family members in astrocytomas and medulloblastomas. Pathol Oncol Res. 2009;15:703-10 pubmed publisher
    ..Differential expression of Notch1, 2, 3, 4 is detected in astrocytomas and medulloblastomas, that may be related to their different roles playing in the development of brain tumors. ..
  7. Tchorz J, Kinter J, Muller M, Tornillo L, Heim M, Bettler B. Notch2 signaling promotes biliary epithelial cell fate specification and tubulogenesis during bile duct development in mice. Hepatology. 2009;50:871-9 pubmed publisher
    ..Notch2 signaling regulates BEC differentiation, the induction of tubulogenesis during IHBD development, and BEC survival. ..
  8. Wu Y, Cain Hom C, Choy L, Hagenbeek T, De Leon G, Chen Y, et al. Therapeutic antibody targeting of individual Notch receptors. Nature. 2010;464:1052-7 pubmed publisher
  9. Frampton G, Coufal M, Li H, Ramirez J, Demorrow S. Opposing actions of endocannabinoids on cholangiocarcinoma growth is via the differential activation of Notch signaling. Exp Cell Res. 2010;316:1465-78 pubmed publisher
    ..The development of novel therapeutic strategies aimed at modulating the endocannabinoid system or mimicking the mode of action of AEA on Notch signaling pathways would prove beneficial for cholangiocarcinoma management. ..
  10. Liu R, Zou L, Fu J, Lu Q. Effects of liquiritigenin treatment on the learning and memory deficits induced by amyloid beta-peptide (25-35) in rats. Behav Brain Res. 2010;210:24-31 pubmed publisher
  11. Kohlhof H, Hampel F, Hoffmann R, Burtscher H, Weidle U, H lzel M, et al. Notch1, Notch2, and Epstein-Barr virus-encoded nuclear antigen 2 signaling differentially affects proliferation and survival of Epstein-Barr virus-infected B cells. Blood. 2009;113:5506-15 pubmed publisher
    ..These findings suggest that Notch signaling in B cells and B-cell lymphomas is only compatible with proliferation if pathways leading to antiapototic signals are active...
  12. Raetzman L, Wheeler B, Ross S, Thomas P, Camper S. Persistent expression of Notch2 delays gonadotrope differentiation. Mol Endocrinol. 2006;20:2898-908 pubmed
    ..This demonstrates that activated Notch2 is sufficient to delay gonadotrope differentiation, and it supports the hypothesis that Notch2 regulates progenitor cell differentiation in the pituitary gland. ..
  13. Gordon W, Vardar Ulu D, L Heureux S, Ashworth T, Malecki M, Sanchez Irizarry C, et al. Effects of S1 cleavage on the structure, surface export, and signaling activity of human Notch1 and Notch2. PLoS ONE. 2009;4:e6613 pubmed publisher
    ..These findings are consistent with models for receptor activation in which ligand-binding or T-ALL-associated mutations lead to conformational changes of the NRR that permit metalloprotease cleavage. ..
  14. Liu Z, Obenauf A, Speicher M, Kopan R. Rapid identification of homologous recombinants and determination of gene copy number with reference/query pyrosequencing (RQPS). Genome Res. 2009;19:2081-9 pubmed publisher
    ..In addition, we also present a simple pyrosequencing-based protocol that could be used for the enrichment of homologous recombinant embryonic stem (ES) cells. ..
  15. Fiorini E, Merck E, Wilson A, Ferrero I, Jiang W, Koch U, et al. Dynamic regulation of notch 1 and notch 2 surface expression during T cell development and activation revealed by novel monoclonal antibodies. J Immunol. 2009;183:7212-22 pubmed publisher
    ..Furthermore they provide an important resource for future analysis of Notch receptors in various tissues including the hematopoietic system. ..
  16. Qiang L, Yang Y, Ma Y, Chen F, Zhang L, Liu W, et al. Isolation and characterization of cancer stem like cells in human glioblastoma cell lines. Cancer Lett. 2009;279:13-21 pubmed publisher
    ..Molecular and functional characterization of such a tumorigenic population may be exploited in the development of novel cancer therapeutic drugs. ..
  17. Schleinitz D, Tonjes A, Bottcher Y, Dietrich K, Enigk B, Koriath M, et al. Lack of significant effects of the type 2 diabetes susceptibility loci JAZF1, CDC123/CAMK1D, NOTCH2, ADAMTS9, THADA, and TSPAN8/LGR5 on diabetes and quantitative metabolic traits. Horm Metab Res. 2010;42:14-22 pubmed publisher
    ..This is compatible with the modest effect size of these "second sweep" variants, which will require large-scale association studies on quantitative traits to clarify their role in the pathophysiology of T2D. ..
  18. Siar C, Nakano K, Han P, Nagatsuka H, Ng K, Kawakami T. Differential expression of Notch receptors and their ligands in desmoplastic ameloblastoma. J Oral Pathol Med. 2010;39:552-8 pubmed publisher
  19. Hijioka H, Setoguchi T, Miyawaki A, Gao H, Ishida T, Komiya S, et al. Upregulation of Notch pathway molecules in oral squamous cell carcinoma. Int J Oncol. 2010;36:817-22 pubmed
    ..These findings suggest that inhibition of the Notch pathway suppresses OSCC growth and may be a useful approach for the treatment of patients with OSCC. ..
  20. Gupta S, Li S, Abedin M, Wang L, Schneider E, Najafian B, et al. Effect of Notch activation on the regenerative response to acute renal failure. Am J Physiol Renal Physiol. 2010;298:F209-15 pubmed publisher
    ..In conclusion, activation of the Notch pathway occurs following ARF. Pretreatment with the Notch ligand DLL4 enhanced recovery from ARF and represents a potential novel therapeutic option for regenerating the injured kidney. ..
  21. Sun H, Kawashima N, Xu J, Takahashi S, Suda H. Expression of Notch signalling-related genes in normal and differentiating rat dental pulp cells. Aust Endod J. 2010;36:54-8 pubmed publisher
    ..These findings suggest that Hey1 may be a negative regulator in odontoblast differentiation. ..
  22. Manaster I, Gazit R, Goldman Wohl D, Stern Ginossar N, Mizrahi S, Yagel S, et al. Notch activation enhances IFNgamma secretion by human peripheral blood and decidual NK cells. J Reprod Immunol. 2010;84:1-7 pubmed publisher
    ..Finally, we show that Notch activation in these cells leads to increased secretion of IFNgamma. We therefore present here a new function of the Notch receptors as enhancers of peripheral blood NK cell and decidual NK cell functions. ..
  23. Hubmann R, Düchler M, Schnabl S, Hilgarth M, Demirtas D, Mitteregger D, et al. NOTCH2 links protein kinase C delta to the expression of CD23 in chronic lymphocytic leukaemia (CLL) cells. Br J Haematol. 2010;148:868-78 pubmed publisher
    ..These data suggest that deregulation of NOTCH2 signalling is critically involved in maintaining the malignant phenotype of CLL lymphocytes and point to a link between PKC-delta and NOTCH2 signalling in the leukemic cells. ..
  24. Pillai S, Cariappa A. The follicular versus marginal zone B lymphocyte cell fate decision. Nat Rev Immunol. 2009;9:767-77 pubmed publisher
    ..This cell fate decision could provide mechanistic insights that are relevant to other commitment events in lymphocytes. ..
  25. Wang J, Wakeman T, Lathia J, Hjelmeland A, Wang X, White R, et al. Notch promotes radioresistance of glioma stem cells. Stem Cells. 2010;28:17-28 pubmed publisher
    ..Taken together, our results suggest a critical role of Notch signaling to regulate radioresistance of glioma stem cells. Inhibition of Notch signaling holds promise to improve the efficiency of current radiotherapy in glioma treatment. ..
  26. Quillard T, Devalliere J, Coupel S, Charreau B. Inflammation dysregulates Notch signaling in endothelial cells: implication of Notch2 and Notch4 to endothelial dysfunction. Biochem Pharmacol. 2010;80:2032-41 pubmed publisher
    ..Thus, here we provide evidence for a role of soluble mediators of inflammation (i.e. cytokines) in the regulation of Notch signaling and for the implication of a dysregulated Notch pathway to endothelial and vascular dysfunction. ..
  27. Mazur P, Einwächter H, Lee M, Sipos B, Nakhai H, Rad R, et al. Notch2 is required for progression of pancreatic intraepithelial neoplasia and development of pancreatic ductal adenocarcinoma. Proc Natl Acad Sci U S A. 2010;107:13438-43 pubmed publisher
    ..Our study supports the concept of distinctive roles of individual Notch receptors in cancer development. ..
  28. Surendran K, Boyle S, Barak H, Kim M, Stomberski C, McCright B, et al. The contribution of Notch1 to nephron segmentation in the developing kidney is revealed in a sensitized Notch2 background and can be augmented by reducing Mint dosage. Dev Biol. 2010;337:386-95 pubmed publisher
  29. Liu R, Zou L, Fu J, Lu Q. Promotion of rat brain-derived progenitor cell neurogenesis by liquiritigenin treatment: underlying mechanisms. Neurosci Lett. 2010;481:139-43 pubmed publisher
  30. Zuniga E, Stellabotte F, Crump J. Jagged-Notch signaling ensures dorsal skeletal identity in the vertebrate face. Development. 2010;137:1843-52 pubmed publisher
    ..We further show that jag1b is expressed specifically in dorsal skeletal precursors, where it acts through the Notch2 receptor to activate hey1 expression...
  31. Ma D, Dai J, Zhu X, Yan S, Zhao P, Zhang J, et al. Aberrant expression of Notch signaling molecules in patients with immune thrombocytopenic purpura. Ann Hematol. 2010;89:155-61 pubmed publisher
    ..Our findings suggest that the aberrant expression profile of Notch pathway may be involved in ITP, and blockage of Notch1 pathway is likely a promising therapeutic concept. ..
  32. Alberi L, Chi Z, Kadam S, Mulholland J, Dawson V, Gaiano N, et al. Neonatal stroke in mice causes long-term changes in neuronal Notch-2 expression that may contribute to prolonged injury. Stroke. 2010;41:S64-71 pubmed publisher
    ..These results suggest that Notch-2 up-regulation after neonatal ischemia is detrimental to neuronal survival. ..
  33. Cao F, Hata R, Zhu P, Nakashiro K, Sakanaka M. Conditional deletion of Stat3 promotes neurogenesis and inhibits astrogliogenesis in neural stem cells. Biochem Biophys Res Commun. 2010;394:843-7 pubmed publisher
    ..Consequently, qPCR analysis showed that elimination of Stat3 in NSC promoted neurogenesis and inhibited astrogliogenesis through down-regulation of notch1, notch2 and hes5, but not hes1 mRNA expression. ..
  34. Fujimura S, Jiang Q, Kobayashi C, Nishinakamura R. Notch2 activation in the embryonic kidney depletes nephron progenitors. J Am Soc Nephrol. 2010;21:803-10 pubmed publisher
  35. Butler J, Nolan D, Vertes E, Varnum Finney B, Kobayashi H, Hooper A, et al. Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells. Cell Stem Cell. 2010;6:251-64 pubmed publisher
    ..Gfp(+) LT-HSCs. ECs establish an instructive vascular niche for clinical-scale expansion of LT-HSCs and a cellular platform to identify stem cell-active trophogens. ..
  36. Gibb D, El Shikh M, Kang D, Rowe W, El Sayed R, Cichy J, et al. ADAM10 is essential for Notch2-dependent marginal zone B cell development and CD23 cleavage in vivo. J Exp Med. 2010;207:623-35 pubmed publisher
    ..Development of MZBs is dependent on Notch2 signaling, which requires proteolysis of the Notch2 receptor by a previously unidentified proteinase...
  37. Quillard T, Devalliere J, Chatelais M, Coulon F, Séveno C, Romagnoli M, et al. Notch2 signaling sensitizes endothelial cells to apoptosis by negatively regulating the key protective molecule survivin. PLoS ONE. 2009;4:e8244 pubmed publisher
    ..Overall, our findings also indicate that specific Notch receptors control distinct functions in vascular cells and inflammatory cytokines contribute to this specificity. ..
  38. Bastide K, Ugolin N, Levalois C, Bernaudin J, Chevillard S. Are adenosquamous lung carcinomas a simple mix of adenocarcinomas and squamous cell carcinomas, or more complex at the molecular level?. Lung Cancer. 2010;68:1-9 pubmed publisher
  39. Fu Y, Edvardsen H, Kaushiva A, Arhancet J, Howe T, Kohaar I, et al. NOTCH2 in breast cancer: association of SNP rs11249433 with gene expression in ER-positive breast tumors without TP53 mutations. Mol Cancer. 2010;9:113 pubmed publisher
    ..Further studies are needed to investigate possible mechanisms of regulation of NOTCH2 expression by rs11249433 and the role of NOTCH2 splicing forms in breast cancer development. ..
  40. Bouhallier F, Allioli N, Lavial F, Chalmel F, Perrard M, Durand P, et al. Role of miR-34c microRNA in the late steps of spermatogenesis. RNA. 2010;16:720-31 pubmed publisher
    ..These data suggest that miR-34c could play a role by enhancing the germinal phenotype of cells already committed to this lineage. ..