notch receptors


Summary: A family of conserved cell surface receptors that contain EPIDERMAL GROWTH FACTOR repeats in their extracellular domain and ANKYRIN REPEATS in their cytoplasmic domains. The cytoplasmic domains are released upon ligand binding and translocate to the CELL NUCLEUS, where they act as transcription factors.

Top Publications

  1. 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
    ..gamma-secretase inhibitors (GSIs) have progressed into the clinic, GSIs fail to distinguish individual Notch receptors, inhibit other signalling pathways and cause intestinal toxicity, attributed to dual inhibition of Notch1 and ..
  2. Ma J, Meng Y, Kwiatkowski D, Chen X, Peng H, Sun Q, et al. Mammalian target of rapamycin regulates murine and human cell differentiation through STAT3/p63/Jagged/Notch cascade. J Clin Invest. 2010;120:103-14 pubmed publisher
    ..Additionally, the STAT3/p63/Notch axis may be a useful target for the treatment of cancers exhibiting hyperactive mTOR signaling. ..
  3. Wright D, Ferjentsik Z, Chong S, Qiu X, Yun Jin J, Malapert P, et al. Cyclic Nrarp mRNA expression is regulated by the somitic oscillator but Nrarp protein levels do not oscillate. Dev Dyn. 2009;238:3043-3055 pubmed publisher
    ..Despite oscillating mRNA levels, Nrarp protein does not oscillate in the PSM. Finally, neither gain nor loss of Nrarp function interferes with the normal expression of Notch-related cyclic genes. ..
  4. Nagel S, Venturini L, Przybylski G, Grabarczyk P, Meyer C, Kaufmann M, et al. NK-like homeodomain proteins activate NOTCH3-signaling in leukemic T-cells. BMC Cancer. 2009;9:371 pubmed publisher
    ..Our data suggest that reduction of NOTCH3-signaling by physiological downregulation of MSX2 expression during T-cell development is abrogated by ectopic expression of oncogenic NKLs, substituting MSX2 function. ..
  5. Benedito R, Roca C, Sörensen I, Adams S, Gossler A, Fruttiger M, et al. The notch ligands Dll4 and Jagged1 have opposing effects on angiogenesis. Cell. 2009;137:1124-35 pubmed publisher
  6. Chanet S, Vodovar N, Mayau V, Schweisguth F. Genome engineering-based analysis of Bearded family genes reveals both functional redundancy and a nonessential function in lateral inhibition in Drosophila. Genetics. 2009;182:1101-8 pubmed publisher
    ..We propose that inhibition of Neur-Delta interaction by Brd family members is part of the feedback loop that underlies lateral inhibition in Drosophila...
  7. Ferjentsik Z, Hayashi S, Dale J, Bessho Y, Herreman A, De Strooper B, et al. Notch is a critical component of the mouse somitogenesis oscillator and is essential for the formation of the somites. PLoS Genet. 2009;5:e1000662 pubmed publisher
    ..We propose that, at least in the mouse embryo, Notch activity is absolutely essential for the formation of a segmented body axis. ..
  8. Oginuma M, Takahashi Y, Kitajima S, Kiso M, Kanno J, Kimura A, et al. The oscillation of Notch activation, but not its boundary, is required for somite border formation and rostral-caudal patterning within a somite. Development. 2010;137:1515-22 pubmed publisher
    ..This indicates that the initial somite pattern can be defined as a direct output of the segmentation clock...
  9. 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
    ..These findings suggest that Notch receptors and their ligands may play differing roles during the development of the desmoplastic ameloblastoma with ..

More Information


  1. Kobayashi T, Mizuno H, Imayoshi I, Furusawa C, Shirahige K, Kageyama R. The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells. Genes Dev. 2009;23:1870-5 pubmed publisher
  2. Okamoto M, Matsuda H, Joetham A, Lucas J, Domenico J, Yasutomo K, et al. Jagged1 on dendritic cells and Notch on CD4+ T cells initiate lung allergic responsiveness by inducing IL-4 production. J Immunol. 2009;183:2995-3003 pubmed publisher
    ..These data identify the essential role of the interactions between Notch on CD4(+) T cells and Jagged1 on APCs in the initiation of IL-4 production and Th2 differentiation for the development of AHR and allergic airway inflammation. ..
  3. 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
    The pathological roles of Notch receptors in renal cell carcinoma (RCC) are still unclear, although Notch receptors have been shown to have an effect on many malignant tumours...
  4. Kopan R, Ilagan M. The canonical Notch signaling pathway: unfolding the activation mechanism. Cell. 2009;137:216-33 pubmed publisher
    ..In this Review, we highlight recent studies in Notch signaling that reveal new molecular details about the regulation of ligand-mediated receptor activation, receptor proteolysis, and target selection. ..
  5. Hayashi S, Shimoda T, Nakajima M, Tsukada Y, Sakumura Y, Dale J, et al. Sprouty4, an FGF inhibitor, displays cyclic gene expression under the control of the notch segmentation clock in the mouse PSM. PLoS ONE. 2009;4:e5603 pubmed publisher
  6. Lewis J, Hanisch A, Holder M. Notch signaling, the segmentation clock, and the patterning of vertebrate somites. J Biol. 2009;8:44 pubmed publisher
    ..The parts it plays in the early operation of the segmentation clock and the later definition and differentiation of the somites are beginning to be understood...
  7. Muto A, Iida A, Satoh S, Watanabe S. The group E Sox genes Sox8 and Sox9 are regulated by Notch signaling and are required for Müller glial cell development in mouse retina. Exp Eye Res. 2009;89:549-58 pubmed publisher
    ..This is the first evidence that group E Sox genes play important roles in the developing vertebrate retina. ..
  8. Mukherjee S, Schaller M, Neupane R, Kunkel S, Lukacs N. Regulation of T cell activation by Notch ligand, DLL4, promotes IL-17 production and Rorc activation. J Immunol. 2009;182:7381-8 pubmed publisher
    ..Thus, facilitation of efficient T cell differentiation may depend upon the activation of T cells via specific notch ligand stimulation. ..
  9. Fortini M. Notch signaling: the core pathway and its posttranslational regulation. Dev Cell. 2009;16:633-47 pubmed publisher
    ..This review describes the core developmental logic of Notch signaling and how regulatory mechanisms tailor Notch pathway outputs to specific developmental scenarios...
  10. Li Y, Takeshita K, Liu P, Satoh M, Oyama N, Mukai Y, et al. Smooth muscle Notch1 mediates neointimal formation after vascular injury. Circulation. 2009;119:2686-92 pubmed publisher
  11. Kazama A, Karashima A, Katayama N, Nakao M. Modeling of segmentation clock mechanism in presomitic mesoderm. Conf Proc IEEE Eng Med Biol Soc. 2009;2009:3267-70 pubmed publisher
    ..The simulation result suggests that the Wnt gradient across the PSM is involved in the dynamics under concern. ..
  12. Surendran K, Selassie M, Liapis H, Krigman H, Kopan R. Reduced Notch signaling leads to renal cysts and papillary microadenomas. J Am Soc Nephrol. 2010;21:819-32 pubmed publisher
  13. Mitsiadis T, Graf D, Luder H, Gridley T, Bluteau G. BMPs and FGFs target Notch signalling via jagged 2 to regulate tooth morphogenesis and cytodifferentiation. Development. 2010;137:3025-35 pubmed publisher
    ..Together, these results demonstrate that Notch signalling mediated by Jag2 is indispensable for normal tooth development...
  14. Chadwick N, Zeef L, Portillo V, Boros J, Hoyle S, van Doesburg J, et al. Notch protection against apoptosis in T-ALL cells mediated by GIMAP5. Blood Cells Mol Dis. 2010;45:201-9 pubmed publisher
  15. Gonçalves R, Martins M, Almeida Porada G, Barbosa M. Induction of notch signaling by immobilization of jagged-1 on self-assembled monolayers. Biomaterials. 2009;30:6879-87 pubmed publisher
    ..In particular, Jag-1-Ab-SAMs have shown to be adequate model surfaces to study Notch pathway activation and may provide a basis to develop new interfaces in biomaterials to control Notch mechanism in different cell systems. ..
  16. Vaccari T, Rusten T, Menut L, Nezis I, Brech A, Stenmark H, et al. Comparative analysis of ESCRT-I, ESCRT-II and ESCRT-III function in Drosophila by efficient isolation of ESCRT mutants. J Cell Sci. 2009;122:2413-23 pubmed publisher
  17. Shepherd A, Wesley U, Wesley C. Notch and delta mRNAs in early-stage and mid-stage drosophila embryos exhibit complementary patterns of protein-producing potentials. Dev Dyn. 2010;239:1220-33 pubmed publisher
    ..Our data also raise the possibility that the manner and regulation of Notch signaling change in the course of embryogenesis and that this change is effected by 3' UTR and mRNA 3' processing factors...
  18. Lin S, Lai S, Yu H, Chihara T, Luo L, Lee T. Lineage-specific effects of Notch/Numb signaling in post-embryonic development of the Drosophila brain. Development. 2010;137:43-51 pubmed publisher
    ..These lineage-specific outputs of Notch/Numb signaling show that a universal mechanism of binary fate decision can be utilized to govern diverse neural sibling differentiations. ..
  19. Nyhan K, Faherty N, Murray G, Cooey L, Godson C, Crean J, et al. Jagged/Notch signalling is required for a subset of TGF?1 responses in human kidney epithelial cells. Biochim Biophys Acta. 2010;1803:1386-95 pubmed publisher
    ..These data suggest that Jagged/Notch signalling is required for a subset of TGF?1-responsive genes, and that complex signalling pathways are involved in the crosstalk between TGF?1 and Notch cascades in kidney epithelia. ..
  20. Cohen M, Georgiou M, Stevenson N, Miodownik M, Baum B. Dynamic filopodia transmit intermittent Delta-Notch signaling to drive pattern refinement during lateral inhibition. Dev Cell. 2010;19:78-89 pubmed publisher
    ..Significantly, the intermittent signaling induced by these filopodial dynamics generates a type of structured noise that is uniquely suited to the generation of well-ordered, tissue-wide epithelial patterns...
  21. Huang Y, Yang X, Wu Y, Jing W, Cai X, Tang W, et al. gamma-secretase inhibitor induces adipogenesis of adipose-derived stem cells by regulation of Notch and PPAR-gamma. Cell Prolif. 2010;43:147-56 pubmed publisher
    ..It may be due to depression of DLK-1/Pref-1 and promotion of de-PPAR-gamma activation, which work through inhibition of Notch-2-Hes-1 pathway by DAPT. ..
  22. Nekanti U, Dastidar S, Venugopal P, Totey S, Ta M. Increased proliferation and analysis of differential gene expression in human Wharton's jelly-derived mesenchymal stromal cells under hypoxia. Int J Biol Sci. 2010;6:499-512 pubmed
    ..Hypoxic WJ-MSCs expressed higher mRNA levels of hypoxia inducible factors, notch receptors and notch downstream gene HES1...
  23. Bonnet A, Dai F, Brand Saberi B, Duprez D. Vestigial-like 2 acts downstream of MyoD activation and is associated with skeletal muscle differentiation in chick myogenesis. Mech Dev. 2010;127:120-36 pubmed publisher
  24. Croce J, McClay D. Dynamics of Delta/Notch signaling on endomesoderm segregation in the sea urchin embryo. Development. 2010;137:83-91 pubmed publisher
    ..Thus, this study provides new insights into the timing mechanisms and the molecular dynamics of endomesoderm segregation during sea urchin embryogenesis and into the mode of action of the Delta/Notch pathway in mediating mesoderm fate...
  25. Strizzi L, Hardy K, Seftor E, Costa F, Kirschmann D, Seftor R, et al. Development and cancer: at the crossroads of Nodal and Notch signaling. Cancer Res. 2009;69:7131-4 pubmed publisher
  26. Akhvlediani T, Henning A, Sandor P, Boesiger P, Jung H. Adaptive metabolic changes in CADASIL white matter. J Neurol. 2010;257:171-7 pubmed publisher
    ..Our data might contribute to the general understanding of adaptive processes induced by hypoperfusion and chronic ischemia. ..
  27. Saj A, Arziman Z, Stempfle D, Van Belle W, Sauder U, Horn T, et al. A combined ex vivo and in vivo RNAi screen for notch regulators in Drosophila reveals an extensive notch interaction network. Dev Cell. 2010;18:862-76 pubmed publisher
    ..Our study reveals a hitherto unappreciated diversity of tissue-specific modulators impinging on Notch and opens new avenues for studying Notch regulation and function in development and disease. ..
  28. Kurosumi M, Nishio Y, Osawa S, Kobayashi H, Iwatsubo T, Tomita T, et al. Novel Notch-sparing gamma-secretase inhibitors derived from a peroxisome proliferator-activated receptor agonist library. Bioorg Med Chem Lett. 2010;20:5282-5 pubmed publisher
    ..Structure-activity relationship studies indicated that (R)-configuration of alpha-substituted phenylpropanoic acid structure and cinnamic acid structure is favorable to prepare Notch-sparing GSIs. ..
  29. Stockhausen M, Kristoffersen K, Poulsen H. The functional role of Notch signaling in human gliomas. Neuro Oncol. 2010;12:199-211 pubmed publisher
    ..In this review, we explore the role of the Notch signaling pathway in gliomas with emphasis on its role in normal brain development and its interplay with pathways and processes that are characteristic of malignant gliomas. ..
  30. Weber J, Calvi L. Notch signaling and the bone marrow hematopoietic stem cell niche. Bone. 2010;46:281-5 pubmed publisher
    ..In this review we discuss the current understanding of Notch signaling and how it functions in hematopoiesis, osteoblastic cells, and the interactions between HSC and their osteoblastic niche. ..
  31. Phillips C, Zuckerman S. CADASIL can mimic multiple sclerosis. J La State Med Soc. 2010;162:174 pubmed
    ..The mutation involves the Notch3 gene which changes a codon for arginine to cysteine at amino acid position 90. ..
  32. Wang Z, Li Y, Kong D, Sarkar F. The role of Notch signaling pathway in epithelial-mesenchymal transition (EMT) during development and tumor aggressiveness. Curr Drug Targets. 2010;11:745-51 pubmed
  33. Windler S, Bilder D. Endocytic internalization routes required for delta/notch signaling. Curr Biol. 2010;20:538-43 pubmed publisher
    ..The absolute requirement for dynamin-dependent endocytosis but not endosomal entry or Rab11 activity supports "pulling force" rather than "recycling" models for Delta activation. ..
  34. Wang Y, Chen Z, Bergmann A. Regulation of EGFR and Notch signaling by distinct isoforms of D-cbl during Drosophila development. Dev Biol. 2010;342:1-10 pubmed publisher
    ..Taken together, these data suggest that D-Cbl controls the EGFR and Notch/Delta signaling pathways through production of two alternatively spliced isoforms during development in Drosophila. ..
  35. Masumura T, Yamamoto K, Shimizu N, Obi S, Ando J. Shear stress increases expression of the arterial endothelial marker ephrinB2 in murine ES cells via the VEGF-Notch signaling pathways. Arterioscler Thromb Vasc Biol. 2009;29:2125-31 pubmed publisher
    ..Exposure to shear stress induces an increase in expression of ephrinB2 in murine ES cells via VEGF-Notch signaling pathways. ..
  36. Willis M, Townley Tilson W, Kang E, Homeister J, Patterson C. Sent to destroy: the ubiquitin proteasome system regulates cell signaling and protein quality control in cardiovascular development and disease. Circ Res. 2010;106:463-78 pubmed publisher
    ..In summary, the crosstalk between the UPS and autophagy highlight the pivotal and diverse roles the UPS plays in maintaining protein quality control and regulating cardiovascular development and disease. ..
  37. Liem M, van der Grond J, Versluis M, Haan J, Webb A, Ferrari M, et al. Lenticulostriate arterial lumina are normal in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy: a high-field in vivo MRI study. Stroke. 2010;41:2812-6 pubmed publisher
    ..The aim of this study is to examine the luminal diameters of lenticulostriate arteries in living patients with CADASIL and to investigate whether luminal narrowing is correlated with the number of lacunar infarcts in the basal ganglia...
  38. Yu Q, Sharma A, Oh S, Moon H, Hossain M, Salay T, et al. T cell factor 1 initiates the T helper type 2 fate by inducing the transcription factor GATA-3 and repressing interferon-gamma. Nat Immunol. 2009;10:992-9 pubmed publisher
    ..Thus, TCF-1 initiates T(H)2 differentiation of activated CD4(+) T cells by promoting GATA-3 expression and suppressing IFN-gamma expression. ..
  39. Wang Z, Li Y, Kong D, Ahmad A, Banerjee S, Sarkar F. Cross-talk between miRNA and Notch signaling pathways in tumor development and progression. Cancer Lett. 2010;292:141-8 pubmed publisher
    ..Further, we summarize how targeting miRNAs by natural agents could become a novel and safer approach for the prevention of tumor progression and treatment. ..
  40. Akiyama J, Okamoto R, Iwasaki M, Zheng X, Yui S, Tsuchiya K, et al. Delta-like 1 expression promotes goblet cell differentiation in Notch-inactivated human colonic epithelial cells. Biochem Biophys Res Commun. 2010;393:662-7 pubmed publisher
    ..Our results suggest a link between Dll1 expression and human goblet cell differentiation that might be mediated by a function that is distinct from its role as a Notch receptor ligand. ..
  41. 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. ..
  42. Efferson C, Winkelmann C, Ware C, Sullivan T, Giampaoli S, Tammam J, et al. Downregulation of Notch pathway by a gamma-secretase inhibitor attenuates AKT/mammalian target of rapamycin signaling and glucose uptake in an ERBB2 transgenic breast cancer model. Cancer Res. 2010;70:2476-84 pubmed publisher
    ..These findings suggest that GSI may provide therapeutic benefit to a subset of ERBB2-positive breast cancers and that [(18)F]FDG-PET imaging may be useful in monitoring clinical response. ..
  43. Rowlinson J, Gering M. Hey2 acts upstream of Notch in hematopoietic stem cell specification in zebrafish embryos. Blood. 2010;116:2046-56 pubmed publisher
    ..These results establish an essential role for Hey2 upstream of Notch in HSC formation. ..
  44. Chari S, Umetsu S, Winandy S. Notch target gene deregulation and maintenance of the leukemogenic phenotype do not require RBP-J kappa in Ikaros null mice. J Immunol. 2010;185:410-7 pubmed publisher
  45. Barad O, Rosin D, Hornstein E, Barkai N. Error minimization in lateral inhibition circuits. Sci Signal. 2010;3:ra51 pubmed publisher
    ..We propose that susceptibility to errors distinguishes seemingly equivalent designs of developmental circuits regulating pattern formation. ..
  46. Brütsch R, Liebler S, Wüstehube J, Bartol A, Herberich S, Adam M, et al. Integrin cytoplasmic domain-associated protein-1 attenuates sprouting angiogenesis. Circ Res. 2010;107:592-601 pubmed publisher
    ..Because CCM1 plays a critical role for cardiovascular development, we hypothesized that its activator ICAP1 is involved in vascular differentiation...
  47. Yan M, Callahan C, Beyer J, Allamneni K, Zhang G, Ridgway J, et al. Chronic DLL4 blockade induces vascular neoplasms. Nature. 2010;463:E6-7 pubmed publisher
    ..Here we show that chronic DLL4 blockade causes pathological activation of endothelial cells, disrupts normal organ homeostasis and induces vascular tumours, raising important safety concerns...
  48. Kelly D, Lake R, Middelkoop T, Fan H, Artavanis Tsakonas S, Walz T. Molecular structure and dimeric organization of the Notch extracellular domain as revealed by electron microscopy. PLoS ONE. 2010;5:e10532 pubmed publisher
    ..These findings open the way to now correlate mutations in the NECD with its oligomeric state and conformation. ..
  49. Lauritsen J, Wong G, Lee S, Lefebvre J, Ciofani M, Rhodes M, et al. Marked induction of the helix-loop-helix protein Id3 promotes the gammadelta T cell fate and renders their functional maturation Notch independent. Immunity. 2009;31:565-75 pubmed publisher
    ..Taken together, these findings identify Id3 as a central player that controls both adoption of the gammadelta fate and its maturation in the thymus. ..
  50. Pan W, Jin Y, STANGER B, Kiernan A. Notch signaling is required for the generation of hair cells and supporting cells in the mammalian inner ear. Proc Natl Acad Sci U S A. 2010;107:15798-803 pubmed publisher
    ..These data indicate that Notch specifies sensory progenitors in the inner ear, and that induction of Notch may be important for regenerating or replacing hair cells and supporting cells in the mammalian inner ear. ..
  51. Stanton M, Hubbs J, Sloman D, Hamblett C, Andrade P, Angagaw M, et al. Fluorinated piperidine acetic acids as gamma-secretase modulators. Bioorg Med Chem Lett. 2010;20:755-8 pubmed publisher
    ..Moreover, in a 7-day safety study, rats treated orally with compound 1f (250mg/kg per day, AUC(0-24)=2100microMh) did not exhibit Notch-related effects. ..
  52. Hartman B, Reh T, Bermingham McDonogh O. Notch signaling specifies prosensory domains via lateral induction in the developing mammalian inner ear. Proc Natl Acad Sci U S A. 2010;107:15792-7 pubmed publisher
    ..These results support a model where activation of Notch and propagation through lateral induction promote prosensory character in specific regions of the developing otocyst. ..
  53. Huang M, Dai Y, Chou Y, Juan Y, Wang C, Chiang B. Regulatory T cells negatively regulate neovasculature of airway remodeling via DLL4-Notch signaling. J Immunol. 2009;183:4745-54 pubmed publisher