Kopan Raphael

Summary

Affiliation: Washington University School of Medicine
Country: USA

Publications

  1. pmc Skin-derived TSLP triggers progression from epidermal-barrier defects to asthma
    Shadmehr Demehri
    Department of Developmental Biology and Division of Dermatology, Washington University School of Medicine, Saint Louis, Missouri, United States of America
    PLoS Biol 7:e1000067. 2009
  2. pmc Molecular insights into segmentation along the proximal-distal axis of the nephron
    Raphael Kopan
    Department of Molecular Biology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Am Soc Nephrol 18:2014-20. 2007
  3. ncbi request reprint Deuterium reveals the dynamics of notch activation
    Kopan Raphael
    Department of Developmental Biology and Division of Dermatology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, St Louis, MO 63110 1095, USA
    Structure 19:443-4. 2011
  4. pmc The canonical Notch signaling pathway: unfolding the activation mechanism
    Raphael Kopan
    Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA
    Cell 137:216-33. 2009
  5. ncbi request reprint Gamma-secretase: proteasome of the membrane?
    Raphael Kopan
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Nat Rev Mol Cell Biol 5:499-504. 2004
  6. ncbi request reprint Analysis of Notch function in presomitic mesoderm suggests a gamma-secretase-independent role for presenilins in somite differentiation
    Stacey S Huppert
    Department of Molecular Biology and Pharmacology, Division of Dermatology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Dev Cell 8:677-88. 2005
  7. ncbi request reprint gamma-secretase functions through Notch signaling to maintain skin appendages but is not required for their patterning or initial morphogenesis
    Yonghua Pan
    Department of Molecular Biology and Pharmacology, Division of Dermatology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Dev Cell 7:731-43. 2004
  8. pmc 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
    Kameswaran Surendran
    Department of Developmental Biology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Dev Biol 337:386-95. 2010
  9. pmc A presenilin dimer at the core of the gamma-secretase enzyme: insights from parallel analysis of Notch 1 and APP proteolysis
    Eric H Schroeter
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 100:13075-80. 2003
  10. pmc Canonical Notch signaling in the developing lung is required for determination of arterial smooth muscle cells and selection of Clara versus ciliated cell fate
    Mitsuru Morimoto
    Department of Developmental Biology and Division of Dermatology, Washington University School of Medicine, Box 8103, Saint Louis, MO 63110 1095, USA
    J Cell Sci 123:213-24. 2010

Research Grants

  1. Mapping Notch 1 Activation in Mice
    Raphael Kopan; Fiscal Year: 2007
  2. Biochemical and Genetic Analysis of Notch Signaling
    Raphael Kopan; Fiscal Year: 2007
  3. Mapping substrate/gamma-secretase interactions
    Raphael Kopan; Fiscal Year: 2007
  4. Role of Notch and Kidney Development
    Raphael Kopan; Fiscal Year: 2007
  5. Biochemical and Genetic Analysis of Notch Signaling
    Raphael Kopan; Fiscal Year: 2009
  6. Mapping substrate/gamma-secretase interactions
    Raphael Kopan; Fiscal Year: 2009
  7. Role of Notch and Kidney Development
    Raphael Kopan; Fiscal Year: 2009
  8. Mapping Notch 1 Activation in Mice
    Raphael Kopan; Fiscal Year: 2006
  9. BIOCHEMICAL ANALYSIS OF NOTCH SIGNAL TRANSDUCTION
    Raphael Kopan; Fiscal Year: 2000
  10. Mapping Notch 1 Activation in Mice
    Raphael Kopan; Fiscal Year: 2003

Collaborators

Detail Information

Publications53

  1. pmc Skin-derived TSLP triggers progression from epidermal-barrier defects to asthma
    Shadmehr Demehri
    Department of Developmental Biology and Division of Dermatology, Washington University School of Medicine, Saint Louis, Missouri, United States of America
    PLoS Biol 7:e1000067. 2009
    ..Based on these findings, we propose that in addition to early treatment of the primary skin-barrier defects, selective inhibition of systemic TSLP may be the key to blocking the development of asthma in AD patients...
  2. pmc Molecular insights into segmentation along the proximal-distal axis of the nephron
    Raphael Kopan
    Department of Molecular Biology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Am Soc Nephrol 18:2014-20. 2007
    ..The underlying principles of regional cell signaling and transcriptional control organizing early segmentation are the subject of this review...
  3. ncbi request reprint Deuterium reveals the dynamics of notch activation
    Kopan Raphael
    Department of Developmental Biology and Division of Dermatology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, St Louis, MO 63110 1095, USA
    Structure 19:443-4. 2011
    ..As predicted from the crystal structure and deletion analyses, the lin-Notch repeats unfold first, facilitating access by ADAM proteases. Surprisingly, the heterodimerization domain remains stable...
  4. pmc The canonical Notch signaling pathway: unfolding the activation mechanism
    Raphael Kopan
    Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA
    Cell 137:216-33. 2009
    ..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. ncbi request reprint Gamma-secretase: proteasome of the membrane?
    Raphael Kopan
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Nat Rev Mol Cell Biol 5:499-504. 2004
  6. ncbi request reprint Analysis of Notch function in presomitic mesoderm suggests a gamma-secretase-independent role for presenilins in somite differentiation
    Stacey S Huppert
    Department of Molecular Biology and Pharmacology, Division of Dermatology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Dev Cell 8:677-88. 2005
    ..These data clarify multiple roles for Notch signaling during segmentation and suggest that the earliest stages of somitogenesis are regulated by both Notch-dependent and Notch-independent functions of presenilin...
  7. ncbi request reprint gamma-secretase functions through Notch signaling to maintain skin appendages but is not required for their patterning or initial morphogenesis
    Yonghua Pan
    Department of Molecular Biology and Pharmacology, Division of Dermatology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Dev Cell 7:731-43. 2004
    ....
  8. pmc 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
    Kameswaran Surendran
    Department of Developmental Biology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Dev Biol 337:386-95. 2010
    ....
  9. pmc A presenilin dimer at the core of the gamma-secretase enzyme: insights from parallel analysis of Notch 1 and APP proteolysis
    Eric H Schroeter
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 100:13075-80. 2003
    ..We propose that gamma-secretase contains a PS dimer in its catalytic core, that binding of substrate is at a site separate from the active site, and that substrate is cleaved at the interface of two PS molecules...
  10. pmc Canonical Notch signaling in the developing lung is required for determination of arterial smooth muscle cells and selection of Clara versus ciliated cell fate
    Mitsuru Morimoto
    Department of Developmental Biology and Division of Dermatology, Washington University School of Medicine, Box 8103, Saint Louis, MO 63110 1095, USA
    J Cell Sci 123:213-24. 2010
    ..These analyses suggest that the impact of gamma-secretase inhibitors on branching in vitro reflect a non-cell autonomous contribution from endothelial or vSMC-derived signals...
  11. ncbi request reprint Notch1 and 2 cooperate in limb ectoderm to receive an early Jagged2 signal regulating interdigital apoptosis
    Yonghua Pan
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, Box 8103, 660 S Euclid Avenue, St Louis, MO 63110, USA
    Dev Biol 286:472-82. 2005
    ..Thus, Notch signaling plays a non-autonomous role in digit septation...
  12. ncbi request reprint Gamma-secretase activity is dispensable for mesenchyme-to-epithelium transition but required for podocyte and proximal tubule formation in developing mouse kidney
    Hui Teng Cheng
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Development 130:5031-42. 2003
    ..These observations suggest that gamma-secretase activity, probably through activation of Notch, is required for maintaining a competent progenitor pool as well as for determining the proximal tubule and podocyte fates...
  13. pmc Epidermal Notch1 loss promotes skin tumorigenesis by impacting the stromal microenvironment
    Shadmehr Demehri
    Department of Developmental Biology, Division of Dermatology, Washington University School of Medicine, Saint Louis, MO 63110 1095, USA
    Cancer Cell 16:55-66. 2009
    ....
  14. pmc Notch and presenilin regulate cellular expansion and cytokine secretion but cannot instruct Th1/Th2 fate acquisition
    Chin Tong Ong
    Department of Developmental Biology, Washington University School of Medicine, Saint Louis, Missouri, United States of America
    PLoS ONE 3:e2823. 2008
    ..The controversies surrounding the role of Notch and presenilins in Th1/Th2 polarization may reflect their role as genetic modifiers of T-helper cells differentiation...
  15. ncbi request reprint Ectodomain shedding and intramembrane cleavage of mammalian Notch proteins is not regulated through oligomerization
    Marc Vooijs
    Department of Molecular Biology and Pharmacology, Division of Dermatology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 279:50864-73. 2004
    ..Our results indicate that ligand-induced reversal of controlled TMD dimerization by the Notch extracellular domain is unlikely to underlie the regulatory mechanism of intramembranous cleavage...
  16. pmc Notch signaling in bulge stem cells is not required for selection of hair follicle fate
    Shadmehr Demehri
    Department of Developmental Biology, Division of Dermatology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Development 136:891-6. 2009
    ..Taken together, our findings yield detailed insight into the function of Notch signaling in hair follicle stem cells and reveal the mechanism of the replacement of Notch-deficient adult hair follicles by epidermal cysts...
  17. pmc Notch-deficient skin induces a lethal systemic B-lymphoproliferative disorder by secreting TSLP, a sentinel for epidermal integrity
    Shadmehr Demehri
    Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri, United States of America
    PLoS Biol 6:e123. 2008
    ..These observations demonstrate that local skin perturbations can drive a lethal systemic disease and have important implications for a wide range of humoral and autoimmune diseases with skin manifestations...
  18. ncbi request reprint Notch pathway is dispensable for adipocyte specification
    Amy M Nichols
    Department of Molecular Biology and Pharmacology and the Department of Medicine Division of Dermatology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Genesis 40:40-4. 2004
    ..We conclude that the "canonical" Notch signaling pathway is dispensable for adipocyte specification and differentiation from either mesenchymal or epithelial progenitors...
  19. ncbi request reprint Aph-2/Nicastrin: an essential component of gamma-secretase and regulator of Notch signaling and Presenilin localization
    Raphael Kopan
    Department of Pharmacology and Molecular Biology, Washington University School of Medicine, St Louis, MO 63110, USA
    Neuron 33:321-4. 2002
    ..The transmembrane protein Nicastrin has been found to associate with Presenilin, Notch, and APP. Recent biochemical and genetic studies have focused on elucidating the function of this protein...
  20. ncbi request reprint Notch: a membrane-bound transcription factor
    Raphael Kopan
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Cell Sci 115:1095-7. 2002
  21. doi request reprint Simple copy number determination with reference query pyrosequencing (RQPS)
    Zhenyi Liu
    Department of Developmental Biology, School of Medicine, Washington University, St Louis, Missouri 63110, USA
    Cold Spring Harb Protoc 2010:pdb.prot5491. 2010
    ....
  22. pmc Gamma-secretase composed of PS1/Pen2/Aph1a can cleave notch and amyloid precursor protein in the absence of nicastrin
    Guojun Zhao
    Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 30:1648-56. 2010
    ..This PS1/Pen2/Aph1a complex, however, is highly unstable. Thus, NCT acts to stabilize gamma-secretase but is not required for substrate recognition...
  23. ncbi request reprint Genetic mosaic analysis indicates that the bulb region of coat hair follicles contains a resident population of several active multipotent epithelial lineage progenitors
    Raphael Kopan
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Dev Biol 242:44-57. 2002
    ..This latter feature resembles the behavior of hematopoietic stem cells after bone marrow transplantation, and raises the question of whether this property may be shared by stem cells in other self-renewing epithelia...
  24. ncbi request reprint Long-range, nonautonomous effects of activated Notch1 on tissue homeostasis in the nail
    Meei Hua Lin
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA
    Dev Biol 263:343-59. 2003
    ..These data support the existence of a novel, cell-nonautonomous role for Notch in maintaining homeostasis of stratified squamous epithelia by indirectly promoting mitosis in basally located cells...
  25. ncbi request reprint A requirement for Notch1 distinguishes 2 phases of definitive hematopoiesis during development
    Brandon K Hadland
    Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis MO 63110, USA
    Blood 104:3097-105. 2004
    ..Thus, Notch1 is required, in a cell-autonomous manner, for the establishment of long-term, definitive hematopoietic stem cells (HSCs)...
  26. pmc Presenilins, Notch dose control the fate of pancreatic endocrine progenitors during a narrow developmental window
    Corentin Cras-Méneur
    Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Genes Dev 23:2088-101. 2009
    ....
  27. ncbi request reprint NOTCH1 regulates osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblast lineage cells
    Shuting Bai
    Departments of Pathology and Immunology, Molecular Biology and Pharmacology, and Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    J Biol Chem 283:6509-18. 2008
    ..These observations raise caution that therapeutic inhibition of NOTCH signaling may adversely accelerate bone loss in humans...
  28. pmc Bi-compartmental communication contributes to the opposite proliferative behavior of Notch1-deficient hair follicle and epidermal keratinocytes
    Jonghyeob Lee
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, Saint Louis, MO 63110, USA
    Development 134:2795-806. 2007
    ..These results suggest that Notch1 participates in a bi-compartmental signaling network that controls homeostasis, follicular proliferation rates and melanocyte population within the skin...
  29. pmc Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron
    Hui Teng Cheng
    Department of Molecular Biology and Pharmacology at Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8103, St Louis, MO 63110, USA
    Development 134:801-11. 2007
    ..These results establish distinct (non-redundant), instructive roles for Notch receptors in nephron segmentation...
  30. pmc Mapping the consequence of Notch1 proteolysis in vivo with NIP-CRE
    Marc Vooijs
    Department of Molecular Biology and Pharmacology and the Department of Medicine, Division of Dermatology, Washington University Medical School, St Louis, MO 63110, USA
    Development 134:535-44. 2007
    ..These findings highlight an underappreciated layer of complexity of Notch signaling in vivo. Moreover, NIP-CRE represents a general strategy applicable for monitoring proteolysis-dependent signaling in vivo...
  31. pmc Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation
    Matthew J Hilton
    Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
    Nat Med 14:306-14. 2008
    ..Thus, mesenchymal progenitors may be expanded in vitro by activating the Notch pathway, whereas bone formation in vivo may be enhanced by transiently suppressing this pathway...
  32. pmc The crystal structure of a partial mouse Notch-1 ankyrin domain: repeats 4 through 7 preserve an ankyrin fold
    Olga Y Lubman
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Protein Sci 14:1274-81. 2005
    ..The structural preservation and stability of the C-terminal repeats shed a new light onto the mechanism of hetero-oligomeric assembly during Notch-mediated transcriptional activation...
  33. ncbi request reprint Analysis of transmembrane domain mutants is consistent with sequential cleavage of Notch by gamma-secretase
    Dilip Chandu
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurochem 96:228-35. 2006
    ..Notch (and perhaps all gamma-secretase substrates) may be cleaved by sequential proteolysis starting at S3...
  34. pmc Genetic interplays between Msx2 and Foxn1 are required for Notch1 expression and hair shaft differentiation
    Jing Cai
    Division of Dermatology, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Dev Biol 326:420-30. 2009
    ..Our results position Msx2 and Foxn1 upstream of Notch1 within the hair matrix and demonstrate that together these factors play a pivotal role in IRS, cortex and medulla differentiation...
  35. ncbi request reprint Target selectivity of vertebrate notch proteins. Collaboration between discrete domains and CSL-binding site architecture determines activation probability
    Chin Tong Ong
    Department of Molecular Biology and Pharmacology, Division of Dermatology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 281:5106-19. 2006
    ....
  36. pmc Rapid identification of homologous recombinants and determination of gene copy number with reference/query pyrosequencing (RQPS)
    Zhenyi Liu
    Department of Developmental Biology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Genome Res 19:2081-9. 2009
    ..In addition, we also present a simple pyrosequencing-based protocol that could be used for the enrichment of homologous recombinant embryonic stem (ES) cells...
  37. pmc rtTA toxicity limits the usefulness of the SP-C-rtTA transgenic mouse
    Mitsuru Morimoto
    Department of Developmental Biology, Division of Dermatology, Washington University School of Medicine, Saint Louis, MO 63110, USA
    Dev Biol 325:171-8. 2009
    ..These studies demonstrate the importance of using appropriate SP-C-rtTA only controls in all experiments...
  38. pmc A faster migrating variant masquerades as NICD when performing in vitro gamma-secretase assays with bacterially expressed Notch substrates
    Preston C Keller
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8231, St Louis, Missouri 63110, USA
    Biochemistry 45:5351-8. 2006
    ....
  39. pmc Reduced Notch signaling leads to renal cysts and papillary microadenomas
    Kameswaran Surendran
    Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Am Soc Nephrol 21:819-32. 2010
    ....
  40. pmc Presenilin: RIP and beyond
    Matthew R Hass
    Department of Developmental Biology, Washington University School of Medicine, Saint Louis, MO, United States
    Semin Cell Dev Biol 20:201-10. 2009
    ..Additionally, we will critically examine the proposed roles of PSEN in the regulation of beta-catenin function, protein trafficking, calcium regulation, and apoptosis...
  41. ncbi request reprint The role of Notch signaling in specification of podocyte and proximal tubules within the developing mouse kidney
    Hui Teng Cheng
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA
    Kidney Int 68:1951-2. 2005
    ....
  42. ncbi request reprint F3/contactin acts as a functional ligand for Notch during oligodendrocyte maturation
    Qi Dong Hu
    Department of Clinical Research, Singapore General Hospital, 169608, Singapore, Singapore
    Cell 115:163-75. 2003
    ..Expression of constitutively active Notch1 or Notch2 does not upregulate MAG. Thus, F3/contactin specifically initiates a Notch/Deltex1 signaling pathway that promotes oligodendrocyte maturation and myelination...
  43. ncbi request reprint Notch and Presenilin: regulated intramembrane proteolysis links development and degeneration
    Dennis Selkoe
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, MA 02115, USA
    Annu Rev Neurosci 26:565-97. 2003
    ..Elucidating the detailed mechanism of Presenilin processing of membrane proteins is important for understanding diverse signal transduction pathways and potentially for treating and preventing Alzheimer's disease...
  44. ncbi request reprint Intramembrane proteolysis: theme and variations
    Michael S Wolfe
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, MA 02115, USA
    Science 305:1119-23. 2004
    ....
  45. ncbi request reprint Notch activation induces apoptosis in neural progenitor cells through a p53-dependent pathway
    Xudong Yang
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Dev Biol 269:81-94. 2004
    ..Together, these complementary gain-of-function and loss-of-function studies reveal a previously unappreciated role of Notch signaling in the regulation of apoptotic cell death during early mammalian neural development...
  46. ncbi request reprint The Notch ligands DLL1 and JAG2 act synergistically to regulate hair cell development in the mammalian inner ear
    Amy E Kiernan
    The Jackson Laboratory, Bar Harbor, ME 04609, USA
    Development 132:4353-62. 2005
    ..Our results demonstrate that the Notch pathway plays a dual role in regulating cellular differentiation and patterning in the cochlea, acting both through lateral inhibition and the control of cellular proliferation...
  47. ncbi request reprint Differentiation and gene regulation: toward a holistic understanding of animal development: intercellular communication and transcriptional regulation are two sides of the same coin
    Alan Michelson
    Curr Opin Genet Dev 12:499-502. 2002
  48. ncbi request reprint Anchoring notch genetics and biochemistry; structural analysis of the ankyrin domain sheds light on existing data
    Olga Y Lubman
    Department of Molecular Biology and Pharmacology and the Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63104 USA
    Mol Cell 13:619-26. 2004
    ....
  49. ncbi request reprint Notch1 signaling influences v2 interneuron and motor neuron development in the spinal cord
    Xudong Yang
    Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
    Dev Neurosci 28:102-17. 2006
    ..These results provide support for a role of Notch1 in neuronal subtype specification in the ventral spinal cord...
  50. ncbi request reprint Potential role of presenilin-regulated signaling pathways in sporadic neurodegeneration
    Edward H Koo
    Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA
    Nat Med 10:S26-33. 2004
    ..In this article, the possibility that these presenilin-regulated molecules may contribute to neurodegeneration is reviewed...
  51. ncbi request reprint Three-dimensional structure of the gamma-secretase complex
    Toshihiko Ogura
    Neuroscience Research Institute and Biological Information Research Center BIRC, National Institute of Advanced Industrial Science and Technology AIST, Umezono 1 1 4, Tsukuba, Ibaraki 305 8568, Japan
    Biochem Biophys Res Commun 343:525-34. 2006
    ..Some of the dimples in the putative transmembrane region may house the catalytic site. The large dimensions are consistent with the observation that gamma-secretase activity resides within a high molecular weight complex...
  52. ncbi request reprint A garden of Notch-ly delights
    Gerry Weinmaster
    Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 1737, USA
    Development 133:3277-82. 2006
    ..Hosted by the Cantoblanco Workshops on Biology and organized by Tom Gridley, José Luis de la Pompa and Juan Carlos Izpisúa Belmonte, the meeting covered diverse aspects of this important signaling pathway...
  53. pmc Quantitative dissection of the Notch:CSL interaction: insights into the Notch-mediated transcriptional switch
    Olga Y Lubman
    T C Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, MD, USA
    J Mol Biol 365:577-89. 2007
    ..These results support an emerging molecular mechanism for the displacement of co-repressors from DNA-bound CSL by NICD...

Research Grants29

  1. Mapping Notch 1 Activation in Mice
    Raphael Kopan; Fiscal Year: 2007
    ..Aim2: Comparison of the developmental potential of N-/- EX cells. Aim3: Analyze conditional loss and gain of function Notchl alleles in the adult. ..
  2. Biochemical and Genetic Analysis of Notch Signaling
    Raphael Kopan; Fiscal Year: 2007
    ..The first two aims are designed to define the TSG activity within the in vivo context and to provide mechanistic clues. The last two aims test mechanistic hypotheses. ..
  3. Mapping substrate/gamma-secretase interactions
    Raphael Kopan; Fiscal Year: 2007
    ..The genetic approach we propose is based on functional complementation assays; we will also conduct HTS screens in a novel assay directly measuring substrate-enzyme interactions. ..
  4. Role of Notch and Kidney Development
    Raphael Kopan; Fiscal Year: 2007
    ..This application Specific Aims to identify Notch-dependent processes and downstream Notch targets during development and during adult kidney regeneration in several renal injury models. ..
  5. Biochemical and Genetic Analysis of Notch Signaling
    Raphael Kopan; Fiscal Year: 2009
    ..The first two aims are designed to define the TSG activity within the in vivo context and to provide mechanistic clues. The last two aims test mechanistic hypotheses. ..
  6. Mapping substrate/gamma-secretase interactions
    Raphael Kopan; Fiscal Year: 2009
    ..The genetic approach we propose is based on functional complementation assays; we will also conduct HTS screens in a novel assay directly measuring substrate-enzyme interactions. ..
  7. Role of Notch and Kidney Development
    Raphael Kopan; Fiscal Year: 2009
    ....
  8. Mapping Notch 1 Activation in Mice
    Raphael Kopan; Fiscal Year: 2006
    ..Aim2: Comparison of the developmental potential of N-/- EX cells. Aim3: Analyze conditional loss and gain of function Notch1 alleles in the adult. ..
  9. BIOCHEMICAL ANALYSIS OF NOTCH SIGNAL TRANSDUCTION
    Raphael Kopan; Fiscal Year: 2000
    ..DESCRIPTION: The Principal Investigator proposes to address the important questions of the mechanisms of intracellular signaling by Notch and the role(s) of Notch in mammalian development. ..
  10. Mapping Notch 1 Activation in Mice
    Raphael Kopan; Fiscal Year: 2003
    ..Aim1: Survey of cells that experience core Notch signaling and express NICD. Aim2: Comparison of the developmental potential of N-/- EX cells. Aim3: Analyze conditional loss and gain of function Notch1 alleles in the adult. ..
  11. Biochemical and Genetic Analysis of Notch Signaling
    Raphael Kopan; Fiscal Year: 2004
    ..To distinguish between inhibition of AB42 production and Notch proteolysis, we propose a novel genetic approach to identify components of the 'y-secretase complex and identify specific blockers of AB42 production. ..
  12. Role of Notch and Kidney Development
    Raphael Kopan; Fiscal Year: 2010
    ....