Y Yarden

Summary

Affiliation: Weizmann Institute of Science
Country: Israel

Publications

  1. pmc Drug-induced ubiquitylation and degradation of ErbB receptor tyrosine kinases: implications for cancer therapy
    Ami Citri
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    EMBO J 21:2407-17. 2002
  2. pmc p38 MAP kinase mediates stress-induced internalization of EGFR: implications for cancer chemotherapy
    Yaara Zwang
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    EMBO J 25:4195-206. 2006
  3. pmc A recombinant decoy comprising EGFR and ErbB-4 inhibits tumor growth and metastasis
    M Lindzen
    Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    Oncogene 31:3505-15. 2012
  4. pmc Modeling ductal carcinoma in situ: a HER2-Notch3 collaboration enables luminal filling
    C R Pradeep
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    Oncogene 31:907-17. 2012
  5. pmc Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression
    F Pareja
    Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    Oncogene 31:4599-608. 2012
  6. pmc Epidermal growth-factor-induced transcript isoform variation drives mammary cell migration
    Wolfgang J Kostler
    Departments of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    PLoS ONE 8:e80566. 2013
  7. pmc Coupled pre-mRNA and mRNA dynamics unveil operational strategies underlying transcriptional responses to stimuli
    Amit Zeisel
    Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel
    Mol Syst Biol 7:529. 2011
  8. pmc Evolvable signaling networks of receptor tyrosine kinases: relevance of robustness to malignancy and to cancer therapy
    Ido Amit
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    Mol Syst Biol 3:151. 2007
  9. doi request reprint Basic cancer research is essential for the success of personalised medicine
    Yosef Yarden
    Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
    Eur J Cancer 49:2619-20. 2013
  10. doi request reprint The ERBB network: at last, cancer therapy meets systems biology
    Yosef Yarden
    Department of Biological Regulation, Weizmann Institute of Science, 1 Hertzl Street, Candiotty Building, Room 312, Rehovot 76100, Israel
    Nat Rev Cancer 12:553-63. 2012

Collaborators

Detail Information

Publications80

  1. pmc Drug-induced ubiquitylation and degradation of ErbB receptor tyrosine kinases: implications for cancer therapy
    Ami Citri
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    EMBO J 21:2407-17. 2002
    ..Based upon a model for drug-induced degradation of ErbB-2, we propose a general strategy for selective destruction of oncoproteins by targeting their interaction with molecular chaperones...
  2. pmc p38 MAP kinase mediates stress-induced internalization of EGFR: implications for cancer chemotherapy
    Yaara Zwang
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    EMBO J 25:4195-206. 2006
    ..Hence, by preventing EGFR-mediated survival signaling, the internalization route we uncovered enhances the cytotoxic effect of drugs like cis-platinum, which may underlie interactions between chemotherapy and EGFR-targeting drugs...
  3. pmc A recombinant decoy comprising EGFR and ErbB-4 inhibits tumor growth and metastasis
    M Lindzen
    Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    Oncogene 31:3505-15. 2012
    ..Taken together, the activities displayed by TRAP-Fc reinforce critical roles of EGF-like growth factors in tumor progression, and they warrant further tests of TRAP-Fc in preclinical models...
  4. pmc Modeling ductal carcinoma in situ: a HER2-Notch3 collaboration enables luminal filling
    C R Pradeep
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    Oncogene 31:907-17. 2012
    ..Therefore, it is conceivable that the integration of the Notch and HER2 signaling pathways contributes to the pathophysiology of DCIS...
  5. pmc Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression
    F Pareja
    Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    Oncogene 31:4599-608. 2012
    ..In conclusion, deubiquitination by Cezanne-1 curtails degradation of growth factor receptors, thereby promotes oncogenic growth signals...
  6. pmc Epidermal growth-factor-induced transcript isoform variation drives mammary cell migration
    Wolfgang J Kostler
    Departments of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    PLoS ONE 8:e80566. 2013
    ..Taken together, our findings highlight the importance of TIV in the rapid evolvement of a phenotypic response to extracellular signals...
  7. pmc Coupled pre-mRNA and mRNA dynamics unveil operational strategies underlying transcriptional responses to stimuli
    Amit Zeisel
    Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel
    Mol Syst Biol 7:529. 2011
    ....
  8. pmc Evolvable signaling networks of receptor tyrosine kinases: relevance of robustness to malignancy and to cancer therapy
    Ido Amit
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    Mol Syst Biol 3:151. 2007
    ..The systems perspective we present views pathologies as hijackers of biological robustness and offers ways for identifying fragile hubs, as well as strategies to overcome drug resistance...
  9. doi request reprint Basic cancer research is essential for the success of personalised medicine
    Yosef Yarden
    Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
    Eur J Cancer 49:2619-20. 2013
    ..Allocating the resources needed for basic studies will likely fuel the next wave of achievements in the long way to conquer cancer. ..
  10. doi request reprint The ERBB network: at last, cancer therapy meets systems biology
    Yosef Yarden
    Department of Biological Regulation, Weizmann Institute of Science, 1 Hertzl Street, Candiotty Building, Room 312, Rehovot 76100, Israel
    Nat Rev Cancer 12:553-63. 2012
    ....
  11. pmc EGR1 and the ERK-ERF axis drive mammary cell migration in response to EGF
    Gabi Tarcic
    Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    FASEB J 26:1582-92. 2012
    ..In summary, EGR1 and the EGF-ERK-ERF axis emerge from our study as major drivers of growth factor-induced mammary cell migration...
  12. ncbi request reprint The EGFR family and its ligands in human cancer. signalling mechanisms and therapeutic opportunities
    Y Yarden
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    Eur J Cancer 37:S3-8. 2001
    ....
  13. ncbi request reprint Biology of HER2 and its importance in breast cancer
    Y Yarden
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    Oncology 61:1-13. 2001
    ..The reported clinical therapeutic efficacy of anti-HER2 monoclonal antibodies in breast cancer highlights the importance of understanding the biology of HER2...
  14. ncbi request reprint Untangling the ErbB signalling network
    Y Yarden
    Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
    Nat Rev Mol Cell Biol 2:127-37. 2001
    ..Likewise, small-molecule enzyme inhibitors and monoclonal antibodies to ErbB1 are in advanced phases of clinical testing. What can this pathway teach us about translating basic science into clinical use?..
  15. ncbi request reprint Molecular approach to breast cancer treatment
    Yosef Yarden
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    Semin Oncol 31:6-13. 2004
    ..Improved molecular characterization and greater understanding of tumorigenesis will enable more individualized treatment...
  16. doi request reprint The biological framework: translational research from bench to clinic
    Yosef Yarden
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    Oncologist 16:23-9. 2011
    ..Complex growth factor signaling networks and novel methods to shut down these networks are described within a framework of engineering and mathematical concepts...
  17. doi request reprint The biological framework: translational research from bench to clinic
    Yosef Yarden
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    Oncologist 15:1-7. 2010
    ..Complex growth factor signaling networks and novel methods to shut down these networks are described within a framework of engineering and mathematical concepts...
  18. ncbi request reprint An immunological approach reveals biological differences between the two NDF/heregulin receptors, ErbB-3 and ErbB-4
    X Chen
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    J Biol Chem 271:7620-9. 1996
    ..These results suggest that homodimers of ErbB-4 are biologically active, but heterodimerization of the kinase-defective ErbB-3, probably with ErbB-2, is essential for transmission of NDF signals through ErbB-3...
  19. pmc A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor
    E Tzahar
    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
    Mol Cell Biol 16:5276-87. 1996
    ..The observed superior ability of ErbB-2 to form heterodimers, in conjunction with its uniquely high basal tyrosine kinase activity, may explain why ErbB-2 overexpression is associated with poor prognosis...
  20. pmc Bivalence of EGF-like ligands drives the ErbB signaling network
    E Tzahar
    Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel
    EMBO J 16:4938-50. 1997
    ..Thus, ligand bivalence enables signal diversification through selective recruitment of homo- and heterodimers of ErbB receptors, and it may explain oncogenicity of erbB-2/HER2...
  21. ncbi request reprint c-Cbl is a suppressor of the neu oncogene
    G Levkowitz
    Departments of Biological Regulation and Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
    J Biol Chem 275:35532-9. 2000
    ..Our results implicate c-Cbl in negative regulation of Neu and offer a potential target for treatment of HER2/ErbB-2-positive human malignancies...
  22. pmc The C-terminus of the kinase-defective neuregulin receptor ErbB-3 confers mitogenic superiority and dictates endocytic routing
    H Waterman
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    EMBO J 18:3348-58. 1999
    ....
  23. ncbi request reprint The fourth immunoglobulin domain of the stem cell factor receptor couples ligand binding to signal transduction
    J M Blechman
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    Cell 80:103-13. 1995
    ..These results identify an intrinsic receptor dimerization site and suggest that similar sites may exist in other receptors...
  24. ncbi request reprint Structure-function analyses of the kit receptor for the steel factor
    J M Blechman
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    Stem Cells 11:12-21. 1993
    ..Further experiments suggested that a putative dimerization site is distinct from the binding cleft and may be located on the fourth Ig-like domain...
  25. ncbi request reprint Defective ubiquitinylation of EGFR mutants of lung cancer confers prolonged signaling
    K Shtiegman
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    Oncogene 26:6968-78. 2007
    ..Our data raise the possibility that refractoriness of L858R-EGFR to downregulation is due to enhanced heterodimerization with the oncogene product HER2, which leads to persistent stimulation...
  26. ncbi request reprint Soluble c-kit proteins and antireceptor monoclonal antibodies confine the binding site of the stem cell factor
    J M Blechman
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    J Biol Chem 268:4399-406. 1993
    ..Hence, the binding site of SCF probably includes Ig-like domains 1 and 2, but structural determinants distal to this portion may also participate in ligand recognition...
  27. ncbi request reprint ErbB-3 mediates differential mitogenic effects of NDF/heregulin isoforms on mouse keratinocytes
    M Marikovsky
    Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel
    Oncogene 10:1403-11. 1995
    ..We conclude that different isoforms of NDF induce distinct growth regulatory effects on cultured keratinocytes, through direct interaction with ErbB-3...
  28. ncbi request reprint Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1
    G Levkowitz
    Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    Mol Cell 4:1029-40. 1999
    ..Our study identifies Cbl proteins as components of the ubiquitin ligation machinery and implies that they similarly suppress many other signaling pathways...
  29. ncbi request reprint Neu differentiation factor inhibits EGF binding. A model for trans-regulation within the ErbB family of receptor tyrosine kinases
    D Karunagaran
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    J Biol Chem 270:9982-90. 1995
    ..This model of negative trans-regulation within the ErbB family is relevant to other subgroups of receptor tyrosine kinases and may have physiological implications...
  30. pmc Neural expression and chromosomal mapping of Neu differentiation factor to 8p12-p21
    A Orr-Urtreger
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    Proc Natl Acad Sci U S A 90:1867-71. 1993
    ..In situ hybridization of a 3H-labeled probe to human metaphase spreads localized the NDF gene to the short arm of chromosome 8 at bands p12-p21...
  31. ncbi request reprint The murine flg gene encodes a receptor for fibroblast growth factor
    A Safran
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    Oncogene 5:635-43. 1990
    ..The latter exhibited progressive cranio-caudal concentration into the intervertebral discs. Taken together, these results strongly suggest that the flg gene encodes a receptor for fibroblast growth factor(s)...
  32. pmc Oncogenic forms of the neu/HER2 tyrosine kinase are permanently coupled to phospholipase C gamma
    E Peles
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    EMBO J 10:2077-86. 1991
    ..Based on the presented results we suggest that the mechanism of cellular transformation by the neu/HER2 receptor involves tyrosine phosphorylation and activation of PLC gamma...
  33. ncbi request reprint Epiregulin is a potent pan-ErbB ligand that preferentially activates heterodimeric receptor complexes
    M Shelly
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    J Biol Chem 273:10496-505. 1998
    ..This remarkable discrepancy between binding affinity and bioactivity is permitted by a mechanism that prevents receptor down-regulation, and results in a weak, but prolonged, state of receptor activation...
  34. ncbi request reprint Neu differentiation factor/neuregulin isoforms activate distinct receptor combinations
    R Pinkas-Kramarski
    Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel
    J Biol Chem 271:19029-32. 1996
    ..These results imply that NDF isoforms differ in their ability to induce receptor heterodimers; whereas both types of isoforms signal through ErbB-3/ErbB-2 heterodimers, only beta isoforms are able to stabilize ErbB-3/ErbB-1 heterodimers...
  35. pmc Modeling invasive breast cancer: growth factors propel progression of HER2-positive premalignant lesions
    C R Pradeep
    Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    Oncogene 31:3569-83. 2012
    ..In conclusion, the integration of a three-dimensional cellular model and clinical data attributes progression of HER2-overexpressing lesions to EGF-like growth factors acting in the context of the tumor's microenvironment...
  36. ncbi request reprint Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor tyrosine kinase
    D Harari
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    Oncogene 18:2681-9. 1999
    ..The primary structure and the pattern of expression of NRG-4, together with the strict specificity of this growth factor to ErbB-4, suggest a physiological role distinct from that of the known ErbB ligands...
  37. ncbi request reprint The ErbB signaling network in embryogenesis and oncogenesis: signal diversification through combinatorial ligand-receptor interactions
    I Alroy
    Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel
    FEBS Lett 410:83-6. 1997
    ..The resulting signaling network has important implications for embryonic development and malignant transformation...
  38. ncbi request reprint Developmental expression of c-kit, a proto-oncogene encoded by the W locus
    A Orr-Urtreger
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    Development 109:911-23. 1990
    ..Correlation between W phenotypes and c-kit expression, as well as the regulation of the complex and multiple expression of polypeptide growth factors and receptors, is discussed...
  39. ncbi request reprint PCR-based identification of new receptors: molecular cloning of a receptor for fibroblast growth factors
    V Raz
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    Oncogene 6:753-60. 1991
    ..We therefore expect that the methodology we developed will enable the study of new receptors in hardly accessible biological systems such as early mammalian embryos or stem cells...
  40. ncbi request reprint The RING finger of c-Cbl mediates desensitization of the epidermal growth factor receptor
    H Waterman
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    J Biol Chem 274:22151-4. 1999
    ..Our results attribute to the RING finger of c-Cbl a causative role in endocytic sorting of EGFR and desensitization of signal transduction...
  41. ncbi request reprint Coupling of the c-Cbl protooncogene product to ErbB-1/EGF-receptor but not to other ErbB proteins
    G Levkowitz
    Department of Chemical Immunology, The Weizmann Institute of Science, Rehovot, Israel
    Oncogene 12:1117-25. 1996
    ..These results indicate that different ErbB proteins can couple to distinct signaling pathways, and therefore their physiological functions are probably non-redundant...
  42. pmc Neu differentiation factor stimulates phosphorylation and activation of the Sp1 transcription factor
    I Alroy
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    Mol Cell Biol 19:1961-72. 1999
    ..Moreover, Sp1 seems to act downstream of all members of the ErbB family and thus may funnel the signaling of the ErbB network into the nucleus...
  43. ncbi request reprint Steel factor and c-kit protooncogene: genetic lessons in signal transduction
    S Lev
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    Crit Rev Oncog 5:141-68. 1994
    ..Predictably, the lessons learned with Kit and Sl mice will be widely relevant to other pairs of ligands and receptors that control the function of different cell lineages and physiological processes...
  44. ncbi request reprint Regulated coupling of the Neu receptor to phosphatidylinositol 3'-kinase and its release by oncogenic activation
    E Peles
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    J Biol Chem 267:12266-74. 1992
    ..Hence, we concluded that phosphatidylinositol 3'-kinase is a physiological substrate of the Neu receptor, but the regulation of this coupling is released upon oncogenic activation...
  45. pmc EGFRvIV: a previously uncharacterized oncogenic mutant reveals a kinase autoinhibitory mechanism
    G Pines
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    Oncogene 29:5850-60. 2010
    ..This information, along with remarkable sensitivities to tyrosine kinase blockers and to a chaperone inhibitor, proposes strategies for pharmacological interception in brain tumors harboring EGFRvIV mutations...
  46. ncbi request reprint The basic biology of HER2
    I Rubin
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    Ann Oncol 12:S3-8. 2001
    ..The recombinant human anti-HER2 monoclonal antibody (rhuMAb-HER2, trastuzumab, Herceptin) induces rapid removal of HER2 from the cell surface, thereby reducing its availability to heterodimers and reducing oncogenicity...
  47. ncbi request reprint Insulin and insulinomimetic agents induce activation of phosphatidylinositol 3'-kinase upon its association with pp185 (IRS-1) in intact rat livers
    Y R Hadari
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    J Biol Chem 267:17483-6. 1992
    ..The recruitment of the holoenzyme may also involve its enzymatic activation and thus constitute an important step in the transduction of insulin signals...
  48. pmc Combining epitope-distinct antibodies to HER2: cooperative inhibitory effects on invasive growth
    A Emde
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    Oncogene 30:1631-42. 2011
    ..Hence, combining mAbs offers a therapeutic strategy, potentially able to enhance clinical efficacy of existing antireceptor immunotherapeutics...
  49. pmc c-Cbl/Sli-1 regulates endocytic sorting and ubiquitination of the epidermal growth factor receptor
    G Levkowitz
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    Genes Dev 12:3663-74. 1998
    ..These results reveal an endosomal sorting machinery capable of controlling the fate, and, hence, signaling potency, of growth factor receptors...
  50. ncbi request reprint Molecular mechanisms underlying endocytosis and sorting of ErbB receptor tyrosine kinases
    H Waterman
    Department of Biological Regulation, The Weizmann Institute of Science, 76100, Rehovot, Israel
    FEBS Lett 490:142-52. 2001
    ..The involvement of other molecules is reviewed and recent observations that challenge the negative regulatory role of endocytosis are described. Finally, we discuss the relevance of receptor down regulation to cancer therapy...
  51. ncbi request reprint The murine vik gene (chromosome 9) encodes a putative receptor with unique protein kinase motifs
    Z Kelman
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    Oncogene 8:37-44. 1993
    ..The unique structural landmarks of vik at both the extracellular and the cytoplasmic domains suggest novel ligand as well as substrate specificity of the presumed receptor...
  52. ncbi request reprint A recombinant ectodomain of the receptor for the stem cell factor (SCF) retains ligand-induced receptor dimerization and antagonizes SCF-stimulated cellular responses
    S Lev
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    J Biol Chem 267:10866-73. 1992
    ..These results indicate that the recombinant ectodomain of the Kit-SCF receptor can be used as a specific antagonist of SCF actions and may enable detailed molecular analysis of ligand-receptor interactions...
  53. ncbi request reprint The ErbB-2/HER2 oncogenic receptor of adenocarcinomas: from orphanhood to multiple stromal ligands
    E Tzahar
    Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    Biochim Biophys Acta 1377:M25-37. 1998
    ..This effect, in turn, may promote the growth of carcinoma cells...
  54. ncbi request reprint Developmental expression of two murine fibroblast growth factor receptors, flg and bek
    A Orr-Urtreger
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    Development 113:1419-34. 1991
    ..The role of bek and flg in gastrulation and in epithelial-mesenchymal interactions of organogenesis will be discussed...
  55. pmc Suppression and promotion of tumor growth by monoclonal antibodies to ErbB-2 differentially correlate with cellular uptake
    E Hurwitz
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    Proc Natl Acad Sci U S A 92:3353-7. 1995
    ..These conclusions are relevant to the selection of optimal mAbs for immunotherapy and may have implications for the mechanism of cellular transformation by an overexpressed erbB-2 gene...
  56. ncbi request reprint Isolation of the neu/HER-2 stimulatory ligand: a 44 kd glycoprotein that induces differentiation of mammary tumor cells
    E Peles
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    Cell 69:205-16. 1992
    ..We propose the name Neu differentiation factor (NDF) for p44...
  57. ncbi request reprint Flg-2, a new member of the family of fibroblast growth factor receptors
    A Avivi
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    Oncogene 6:1089-92. 1991
    ..Analysis of mRNA from various tissues shows that flg-2 is expressed predominantly in skin, brain and lung...
  58. pmc Agonistic antibodies stimulate the kinase encoded by the neu protooncogene in living cells but the oncogenic mutant is constitutively active
    Y Yarden
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    Proc Natl Acad Sci U S A 87:2569-73. 1990
    ..This mechanism is deregulated in the oncogenic mutant, which is functionally equivalent to ligand-stimulated receptor...
  59. doi request reprint Receptor tyrosine kinases: the emerging tip of systems control
    R Seger
    Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    IET Syst Biol 2:1-4. 2008
    ..As highlighted below, systems control (a layered web of regulatory loops summarised in Fig.1) emerged throughout the workshop as a common theme of many presentations...
  60. ncbi request reprint [Basic principles of signal transduction]
    Yosef Yarden
    Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    Onkologie 28:14-7. 2005
  61. ncbi request reprint The achilles heel of ErbB-2/HER2: regulation by the Hsp90 chaperone machine and potential for pharmacological intervention
    Ami Citri
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    Cell Cycle 3:51-60. 2004
    ..Hence, the dependence of ErbB-2 upon Hsp90 reveals an Achilles heel, which opens a window of opportunity for combating cancers driven by the ErbB/HER signaling network...
  62. ncbi request reprint Cancer therapeutic antibodies come of age: targeting minimal residual disease
    Tsipi Ben Kasus
    Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
    Mol Oncol 1:42-54. 2007
    ..Here we discuss molecular mechanisms of antibody-based therapy, the emerging ability to target minimal disease and the therapeutic potential of combining antibodies with other modalities...
  63. ncbi request reprint A reciprocal tensin-3-cten switch mediates EGF-driven mammary cell migration
    Menachem Katz
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    Nat Cell Biol 9:961-9. 2007
    ..In conclusion, a transcriptional tensin-3-cten switch may contribute to the metastasis of mammary cancer...
  64. pmc Persistent elimination of ErbB-2/HER2-overexpressing tumors using combinations of monoclonal antibodies: relevance of receptor endocytosis
    Tsipi Ben-Kasus
    Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
    Proc Natl Acad Sci U S A 106:3294-9. 2009
    ..One potential mechanism, namely the ability of mAb combinations to instigate ErbB-2 endocytosis, is demonstrated. Translation of these lessons to clinical applications may enhance patient response and delay acquisition of resistance...
  65. ncbi request reprint Signal transduction and oncogenesis by ErbB/HER receptors
    Mina D Marmor
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    Int J Radiat Oncol Biol Phys 58:903-13. 2004
    ....
  66. ncbi request reprint Oncogenic growth factor receptors: implications for signal transduction therapy
    Yaron Mosesson
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    Semin Cancer Biol 14:262-70. 2004
    ..The underlying mechanisms are critically examined, with an emphasis on potential drug combinations, which hold promise for enhanced clinical efficacy...
  67. pmc Kinase-mediated quasi-dimers of EGFR
    Erez M Bublil
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    FASEB J 24:4744-55. 2010
    ..On the basis of these observations, we propose that quasi-dimers precede formation of ligand-induced, fully active dimers, which are stabilized by both extracellular and intracellular receptor-receptor interactions...
  68. pmc Tailored cancer immunotherapy using combinations of chemotherapy and a mixture of antibodies against EGF-receptor ligands
    Moshit Lindzen
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    Proc Natl Acad Sci U S A 107:12559-63. 2010
    ....
  69. pmc Synergistic down-regulation of receptor tyrosine kinases by combinations of mAbs: implications for cancer immunotherapy
    Lilach M Friedman
    Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
    Proc Natl Acad Sci U S A 102:1915-20. 2005
    ..We present a model attributing efficacy of immunotherapy to the size of Ab-receptor lattices formed at the cell surface, which dictates the rate of endocytic clearance and extent of signaling blockade...
  70. ncbi request reprint Hsp90 recognizes a common surface on client kinases
    Ami Citri
    Department of Biological Regulation, Weizmann Institute of Science, Rehovot 97100, Israel
    J Biol Chem 281:14361-9. 2006
    ..These lessons bear significance to pharmacological attempts to target the chaperone in human pathologies, such as cancer...
  71. pmc Hsp90 restrains ErbB-2/HER2 signalling by limiting heterodimer formation
    Ami Citri
    Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel
    EMBO Rep 5:1165-70. 2004
    ..These results define a role for Hsp90 as a molecular switch regulating the ErbB signalling network by limiting formation of ErbB-2-centred receptor complexes...
  72. ncbi request reprint The deaf and the dumb: the biology of ErbB-2 and ErbB-3
    Ami Citri
    Department of Biological Regulation, The Weizmann Institute of Science, 76100, Rehovot, Israel
    Exp Cell Res 284:54-65. 2003
    ..This review highlights recent structural insights into the mechanism of ligand-induced heterodimer formation, and concentrates on signaling pathways employed by ErbB-2 and ErbB-3 in normal and in malignant cells...
  73. ncbi request reprint Polar expression of ErbB-2/HER2 in epithelia. Bimodal regulation by Lin-7
    Maya Shelly
    Department of Biological Regulation, The Weizmann Institute of Science, 76100, Rehovot, Israel
    Dev Cell 5:475-86. 2003
    ..Hence, distinct domains of Lin-7 regulate receptor delivery to and maintenance at the basolateral surface of epithelia...
  74. ncbi request reprint Epigen, the last ligand of ErbB receptors, reveals intricate relationships between affinity and mitogenicity
    Bose S Kochupurakkal
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    J Biol Chem 280:8503-12. 2005
    ..In conclusion, EPG might represent the last EGF-like growth factor and define a category of low affinity ligands, whose bioactivity differs from the more extensively studied high affinity ligands...
  75. pmc Oncogenic mutant forms of EGFR: lessons in signal transduction and targets for cancer therapy
    Gur Pines
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel
    FEBS Lett 584:2699-706. 2010
    ..Deeper understanding of signaling pathways downstream to mutant receptors will likely improve the outcome of current EGFR-targeted therapies, as well as help develop new drugs and combinations...
  76. ncbi request reprint EGF decreases the abundance of microRNAs that restrain oncogenic transcription factors
    Roi Avraham
    Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel
    Sci Signal 3:ra43. 2010
    ..These findings identify specific microRNAs as attenuators of growth factor signaling and oncogenesis...
  77. ncbi request reprint Hsp90 inhibitor 17-AAG reduces ErbB2 levels and inhibits proliferation of the trastuzumab resistant breast tumor cell line JIMT-1
    Barbara Zsebik
    Department of Biophysics and Cell Biology, Faculty of Medicine, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary
    Immunol Lett 104:146-55. 2006
    ....
  78. ncbi request reprint ErbB-4 may control behavior of prostate cancer cells and serve as a target for molecular therapy
    Rami Ben-Yosef
    Department of Oncology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    Prostate 67:871-80. 2007
    ....
  79. pmc Activation of AMP-activated protein kinase by human EGF receptor 2/EGF receptor tyrosine kinase inhibitor protects cardiac cells
    Neil L Spector
    Duke Comprehensive Cancer Center, Duke University Medical Center, Medical Science Research Building II, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 104:10607-12. 2007
    ....
  80. ncbi request reprint ErbB4 increases the proliferation potential of human lung cancer cells and its blockage can be used as a target for anti-cancer therapy
    Alex Starr
    Lung and Allergy Institute, Tel Aviv Sourasky Medical Center and Tel Aviv University School of Medicine, Tel Aviv, Israel
    Int J Cancer 119:269-74. 2006
    ..The results of the current study provide evidence that ErbB-4 plays a significant role in human lung cancer and may serve as a molecular target for anticancer therapy...

Research Grants10

  1. Next generation strategies to intercept ErbB signaling
    Yosef Yarden; Fiscal Year: 2006
    ..abstract_text> ..
  2. ERBB 2 ERBB 3 HETERODIMERIC RECEPTOR OF CARCINOMAS
    Yosef Yarden; Fiscal Year: 2002
    ..This model will be examined by using mutant receptors, and the recycling machinery characterized in details. The suspected cancer-inhibitory activity of drugs interfering with ErbB routing will be tested in vivo. ..
  3. ERBB 2 ERBB 3 HETERODIMERIC RECEPTOR OF CARCINOMAS
    Yosef Yarden; Fiscal Year: 2003
    ..This model will be examined by using mutant receptors, and the recycling machinery characterized in details. The suspected cancer-inhibitory activity of drugs interfering with ErbB routing will be tested in vivo. ..
  4. ERBB 2 ERBB 3 HETERODIMERIC RECEPTOR OF CARCINOMAS
    Yosef Yarden; Fiscal Year: 2001
    ..This model will be examined by using mutant receptors, and the recycling machinery characterized in details. The suspected cancer-inhibitory activity of drugs interfering with ErbB routing will be tested in vivo. ..
  5. ERBB 2 ERBB 3 HETERODIMERIC RECEPTOR OF CARCINOMAS
    Yosef Yarden; Fiscal Year: 2004
    ..This model will be examined by using mutant receptors, and the recycling machinery characterized in details. The suspected cancer-inhibitory activity of drugs interfering with ErbB routing will be tested in vivo. ..
  6. ERBB 2 ERBB 3 HETERODIMERIC RECEPTOR OF CARCINOMAS
    Yosef Yarden; Fiscal Year: 2000
    ..This model will be examined by using mutant receptors, and the recycling machinery characterized in details. The suspected cancer-inhibitory activity of drugs interfering with ErbB routing will be tested in vivo. ..
  7. LATERAL VERSUS VERTICAL SIGNALING BY ERBB2 ONCOPROTEIN
    Yosef Yarden; Fiscal Year: 1999
    ....