Shigeki Higashiyama

Summary

Affiliation: Ehime University
Country: Japan

Publications

  1. doi request reprint Membrane-anchored growth factors, the epidermal growth factor family: beyond receptor ligands
    Shigeki Higashiyama
    Department of Biochemistry and Molecular Genetics, Center for Regenerative Medicine CEREM, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791 0295, Japan
    Cancer Sci 99:214-20. 2008
  2. ncbi request reprint Metalloproteinase-mediated shedding of heparin-binding EGF-like growth factor and its pathophysiological roles
    Shigeki Higashiyama
    Division of Biochemistry and Molecular Genetics, Department of Molecular and Cellular Biology, Ehime University School of Medicine Shigenobu, Onsen gun, Ehime, 791 0295, Japan
    Protein Pept Lett 11:443-50. 2004
  3. pmc Proteolytic release of the carboxy-terminal fragment of proHB-EGF causes nuclear export of PLZF
    Daisuke Nanba
    Department of Medical Biochemistry, Ehime University School of Medicine, Onsen gun, Ehime 791 0295, Japan
    J Cell Biol 163:489-502. 2003
  4. pmc Membrane-anchored growth factor, HB-EGF, on the cell surface targeted to the inner nuclear membrane
    Miki Hieda
    Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime 791 0295, Japan
    J Cell Biol 180:763-9. 2008
  5. doi request reprint Lighting up by EMARS
    Shigeki Higashiyama
    Department of Cell Growth and Tumor Regulation, ProteoMedicine Research Center, Ehime University
    J Biochem 152:381-2. 2012
  6. pmc Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion
    Takaya Shimura
    Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho cho, Mizuho ku, Japan
    BMC Cancer 12:205. 2012
  7. pmc Evidence against roles for phorbol binding protein Munc13-1, ADAM adaptor Eve-1, or vesicle trafficking phosphoproteins Munc18 or NSF as phospho-state-sensitive modulators of phorbol/PKC-activated Alzheimer APP ectodomain shedding
    Annat F Ikin
    Farber Institute for Neurosciences of Thomas Jefferson University, 900 Walnut Street, Philadelphia, 19107, PA, USA
    Mol Neurodegener 2:23. 2007
  8. doi request reprint Ectodomain shedding and remnant peptide signalling of EGFRs and their ligands
    Shigeki Higashiyama
    Department of Cell Growth and Tumor Regulation, Proteo Medicine Research Center ProMRes, Ehime University, Japan
    J Biochem 150:15-22. 2011
  9. ncbi request reprint ADAM-mediated ectodomain shedding of HB-EGF in receptor cross-talk
    Shigeki Higashiyama
    Division of Biochemistry and Molecular Genetics, Department of Molecular and Cellular Biology, Ehime University School of Medicine, Shitsukawa, Toon, Ehime 791 0295, Japan
    Biochim Biophys Acta 1751:110-7. 2005
  10. pmc Cell surface annexins regulate ADAM-mediated ectodomain shedding of proamphiregulin
    Hironao Nakayama
    Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
    Mol Biol Cell 23:1964-75. 2012

Detail Information

Publications80

  1. doi request reprint Membrane-anchored growth factors, the epidermal growth factor family: beyond receptor ligands
    Shigeki Higashiyama
    Department of Biochemistry and Molecular Genetics, Center for Regenerative Medicine CEREM, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791 0295, Japan
    Cancer Sci 99:214-20. 2008
    ....
  2. ncbi request reprint Metalloproteinase-mediated shedding of heparin-binding EGF-like growth factor and its pathophysiological roles
    Shigeki Higashiyama
    Division of Biochemistry and Molecular Genetics, Department of Molecular and Cellular Biology, Ehime University School of Medicine Shigenobu, Onsen gun, Ehime, 791 0295, Japan
    Protein Pept Lett 11:443-50. 2004
    ..Antagonizing metalloproteinases can inhibit EGFR transactivation and might be of therapeutic value, for example in cardiac hypertrophy, skin remodeling and tumor growth...
  3. pmc Proteolytic release of the carboxy-terminal fragment of proHB-EGF causes nuclear export of PLZF
    Daisuke Nanba
    Department of Medical Biochemistry, Ehime University School of Medicine, Onsen gun, Ehime 791 0295, Japan
    J Cell Biol 163:489-502. 2003
    ..These results indicate that released HB-EGF-C functions as an intracellular signal and coordinates cell cycle progression with HB-EGF...
  4. pmc Membrane-anchored growth factor, HB-EGF, on the cell surface targeted to the inner nuclear membrane
    Miki Hieda
    Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime 791 0295, Japan
    J Cell Biol 180:763-9. 2008
    ..The dominant-active form of Rab5 and Rab11 suppressed nuclear envelope targeting. Collectively, these data demonstrate that membrane-anchored HB-EGF is targeted to the inner nuclear membrane via a retrograde membrane trafficking pathway...
  5. doi request reprint Lighting up by EMARS
    Shigeki Higashiyama
    Department of Cell Growth and Tumor Regulation, ProteoMedicine Research Center, Ehime University
    J Biochem 152:381-2. 2012
    ..J Biochem 2011;149:347-355). The EMARS reaction is also currently lighting up intriguing new partners of target therapeutic molecules...
  6. pmc Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion
    Takaya Shimura
    Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho cho, Mizuho ku, Japan
    BMC Cancer 12:205. 2012
    ..However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear...
  7. pmc Evidence against roles for phorbol binding protein Munc13-1, ADAM adaptor Eve-1, or vesicle trafficking phosphoproteins Munc18 or NSF as phospho-state-sensitive modulators of phorbol/PKC-activated Alzheimer APP ectodomain shedding
    Annat F Ikin
    Farber Institute for Neurosciences of Thomas Jefferson University, 900 Walnut Street, Philadelphia, 19107, PA, USA
    Mol Neurodegener 2:23. 2007
    ..Here, we examined the effects on APP ectodomain shedding of four phorbol-sensitive proteins involved in regulation of vesicular membrane trafficking of APP: Munc13-1, Munc18, NSF, and Eve-1...
  8. doi request reprint Ectodomain shedding and remnant peptide signalling of EGFRs and their ligands
    Shigeki Higashiyama
    Department of Cell Growth and Tumor Regulation, Proteo Medicine Research Center ProMRes, Ehime University, Japan
    J Biochem 150:15-22. 2011
    ..In addition, the study of the remnant peptide signalling would be essential for understanding the physiological and pathological relevance of anti-shedding therapeutic strategies for diseases such as cancer...
  9. ncbi request reprint ADAM-mediated ectodomain shedding of HB-EGF in receptor cross-talk
    Shigeki Higashiyama
    Division of Biochemistry and Molecular Genetics, Department of Molecular and Cellular Biology, Ehime University School of Medicine, Shitsukawa, Toon, Ehime 791 0295, Japan
    Biochim Biophys Acta 1751:110-7. 2005
    ..Here we focus on the ectodomain shedding of HB-EGF by ADAMs, which is not only a key event of receptor cross-talk but also a novel intercellular signaling by the carboxy-terminal fragment (CTF signal)...
  10. pmc Cell surface annexins regulate ADAM-mediated ectodomain shedding of proamphiregulin
    Hironao Nakayama
    Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
    Mol Biol Cell 23:1964-75. 2012
    ..On the basis of these data, we propose that annexins on the cell surface function as "shedding platform" proteins to determine the substrate selectivity of ADAM17, with possible therapeutic potential in ADAM-related diseases...
  11. ncbi request reprint The carboxyl-terminal fragment of pro-HB-EGF reverses Bcl6-mediated gene repression
    Yumi Kinugasa
    Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Shitsukawa, To on, Ehime 791 0295, Japan
    J Biol Chem 282:14797-806. 2007
    ..These findings suggest that HB-EGF-CTF is a potent regulator of gene expression via its interaction with the transcriptional repressor Bcl6...
  12. ncbi request reprint An intermediary role of proHB-EGF shedding in growth factor-induced c-Myc gene expression
    Daisuke Nanba
    Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
    J Cell Physiol 214:465-73. 2008
    ....
  13. doi request reprint Corneal epithelial wound healing impaired in keratinocyte-specific HB-EGF-deficient mice in vivo and in vitro
    Ryuji Yoshioka
    Department of Ophthalmology, Ehime University Graduate School of Medicine, Ehime, Japan
    Invest Ophthalmol Vis Sci 51:5630-9. 2010
    ..To study the role played by HB-EGF in corneal epithelial wound healing...
  14. ncbi request reprint Human corneal epithelial cell proliferation by epiregulin and its cross-induction by other EGF family members
    Shin ichi Morita
    Department of Ophthalmology, Ehime University School of Medicine, Ehime, Japan
    Mol Vis 13:2119-28. 2007
    ..To investigate the effects of epiregulin, a newly identified member of the epidermal growth factor (EGF) family, on the proliferation of human corneal epithelial cells (HCECs)...
  15. ncbi request reprint Loss of HB-EGF in smooth muscle or endothelial cell lineages causes heart malformation
    Daisuke Nanba
    Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Shitsukawa, To on, Ehime 791 0295, Japan
    Biochem Biophys Res Commun 350:315-21. 2006
    ..These results suggest that expression of HB-EGF in smooth muscle and/or endothelial cell lineages is essential for proper heart development and function in mice...
  16. pmc Human antigen R-mediated mRNA stabilization is required for ultraviolet B-induced autoinduction of amphiregulin in keratinocytes
    Hironao Nakayama
    Department of Biochemistry and Molecular Genetics, Ehime University, Shitsukawa, Toon, Ehime 791 0295, Japan
    J Biol Chem 288:10338-48. 2013
    ....
  17. doi request reprint Protein kinase D2 and heat shock protein 90 beta are required for BCL6-associated zinc finger protein mRNA stabilization induced by vascular endothelial growth factor-A
    Daisuke Miwa
    Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791 0295, Japan
    Angiogenesis 16:675-88. 2013
    ..These data suggest that HSP90β may positively regulate angiogenesis, not only as a protein chaperone, but also as an mRNA stabilizer for pro-angiogenic genes, such as BAZF, in a PRKD2 activity-dependent manner...
  18. ncbi request reprint Ectodomain shedding of membrane-anchored heparin-binding EGF like growth factor and subcellular localization of the C-terminal fragment in the cell cycle
    Fujio Toki
    Department of Molecular and Cellular Biology, Division of Biochemistry and Molecular Genetics, Ehime University School of Medicine, Shitsukawa, Shigenobu cho, Onsen gun, Ehime, Japan
    J Cell Physiol 202:839-48. 2005
    ....
  19. doi request reprint BAZF, a novel component of cullin3-based E3 ligase complex, mediates VEGFR and Notch cross-signaling in angiogenesis
    Hidetaka Ohnuki
    Department of Biochemistry and Molecular Genetics, Ehime University, Ehime, Japan
    Blood 119:2688-98. 2012
    ..We therefore propose that BAZF supports angiogenic sprouting via BAZF-CUL3-based polyubiquitination-dependent degradation of CBF1 to down-regulate Notch signaling...
  20. ncbi request reprint Overexpression of ADAM9 enhances growth factor-mediated recycling of E-cadherin in human colon cancer cell line HT29 cells
    Takafumi Hirao
    Division of Biochemistry and Molecular Genetics, Department of Molecular and Cellular Biology, Ehime University School of Medicine, Ehime 791 0295, Japan
    Exp Cell Res 312:331-9. 2006
    ..These results suggest that the metalloprotease activity of ADAM9 mediates growth factor-induced endocytosis and dynamic recycling of E-cadherin and prevents E-cadherin degradation...
  21. doi request reprint Plasma-membrane-anchored growth factor pro-amphiregulin binds A-type lamin and regulates global transcription
    Mayumi Isokane
    Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Toon, Ehime 791 0295, Japan
    J Cell Sci 121:3608-18. 2008
    ....
  22. ncbi request reprint Recent advances in the epidermal growth factor receptor/ligand system biology on skin homeostasis and keratinocyte stem cell regulation
    Daisuke Nanba
    Senior Research Fellow Center, Ehime University, Shitsukawa, Toon, Ehime 791 0295, Japan Department of Cell Growth and Tumor Regulation, Proteo Science Center PROS, Ehime University, Shitsukawa, Toon, Ehime 791 0295, Japan Electronic address
    J Dermatol Sci 72:81-6. 2013
    ..We present an overview of the recent progress in the field of the EGF receptor/ligand system on skin homeostasis and regulation of keratinocyte stem cells. ..
  23. ncbi request reprint Roles of charged amino acid residues in the cytoplasmic domain of proHB-EGF
    Daisuke Nanba
    Division of Biochemistry and Molecular Genetics, Department of Molecular and Cellular Biology, Ehime University School of Medicine, Shitsukawa, Shigenobu cho, Onsen gun, Ehime 791 0295, Japan
    Biochem Biophys Res Commun 320:376-82. 2004
    ..Further, the charged amino acids are also required for HB-EGF-C-PLZF interaction. These results indicate that the cytoplasmic domain of proHB-EGF is a multifunctional domain...
  24. doi request reprint Spatiotemporal visualization of proHB-EGF ectodomain shedding in living cells
    Hirofumi Inoue
    Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791 0295, Japan
    J Biochem 154:67-76. 2013
    ..Fluhemb might be very useful for detecting the activity of proHB-EGF shedding in various types of cells under different conditions in vitro and in vivo. ..
  25. ncbi request reprint Dual intracellular signaling by proteolytic cleavage of membrane-anchored heparin-binding EGF-like growth factor
    Daisuke Nanba
    Department of Medical Biochemistry, Ehime University School of Medicine, Shitsukawa, Shigenobu cho, Onsen gun, Ehime 791 0295, Japan
    Cytokine Growth Factor Rev 15:13-9. 2004
    ..ProHB-EGF generates dual intracellular signaling molecules by its proteolytic cleavage...
  26. ncbi request reprint PLZF regulates Pbx1 transcription and Pbx1-HoxC8 complex leads to androgen-independent prostate cancer proliferation
    Tadahiko Kikugawa
    Department of Biochemistry and Molecular Genetics, Ehime University School of Medicine, Shitsukawa, To on, Ehime, Japan
    Prostate 66:1092-9. 2006
    ..DU145 cells show androgen-independent growth and lack PLZF gene expression...
  27. doi request reprint Monoubiquitination of pro-amphiregulin regulates its endocytosis and ectodomain shedding
    Shinji Fukuda
    Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791 0295, Japan
    Biochem Biophys Res Commun 420:315-20. 2012
    ..These results suggested that pro-AREG monoubiquitination and the subsequent trafficking to intracellular organelles is a novel shedding regulatory mechanism that contributes to the secretion of EGFR ligands in growth factor signaling...
  28. ncbi request reprint Heparin-binding EGF-like growth factor accelerates keratinocyte migration and skin wound healing
    Yuji Shirakata
    Department of Dermatology, Ehime University School of Medicine, Ehime 791 0295, Japan
    J Cell Sci 118:2363-70. 2005
    ....
  29. ncbi request reprint Role of promyelocytic leukemia zinc finger protein in proliferation of cultured human corneal endothelial cells
    Atsushi Shiraishi
    Department of Ophthalmology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791 0295, Japan
    Cornea 26:S55-8. 2007
    ..To review the role of promyelocytic leukemia zinc finger (PLZF), a transcriptional repressor and negative regulator of cell cycling, in the proliferation of cultured human corneal endothelial cells (HCECs)...
  30. doi request reprint Important role of epiregulin in inflammatory responses during corneal epithelial wound healing
    Yuan Zhang
    Department of Ophthalmology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
    Invest Ophthalmol Vis Sci 53:2414-23. 2012
    ..To investigate the role played by epiregulin in corneal epithelial wound healing in vivo in epiregulin-knockout (KO) mice and cultured mouse corneal epithelial cells (MCECs)...
  31. doi request reprint Fibronectin regulates proteoglycan production balance in transforming growth factor-β1-induced chondrogenesis
    Tatsuhiko Kutsuna
    Department of Bone and Joint Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
    Int J Mol Med 28:829-34. 2011
    ..These data suggest that fibronectin is a critical mediator for TGF-β-specific production balance of 2 major proteoglycans, aggrecan and versican, during chondrogenesis...
  32. ncbi request reprint Induction of keratinocyte migration via transactivation of the epidermal growth factor receptor by the antimicrobial peptide LL-37
    Sho Tokumaru
    Department of Dermatology, Ehime University School of Medicine, Ehime, Japan
    J Immunol 175:4662-8. 2005
    ..The results of this study suggest that LL-37 closes skin wounds by the induction of keratinocyte migration...
  33. ncbi request reprint Activation of epidermal growth factor receptor gene is involved in transforming growth factor-beta-mediated fibronectin expression in a chondrocyte progenitor cell line
    Haruhiko Takeda
    Department of Bone and Joint Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791 0295, Japan
    Int J Mol Med 25:593-600. 2010
    ..These data indicated that Egfr gene activation by TGF-beta is involved in the differences in the expression of cellular matrix genes such as Fn, as compared to the expression pattern induced by BMPs...
  34. ncbi request reprint ADAM binding protein Eve-1 is required for ectodomain shedding of epidermal growth factor receptor ligands
    Motonari Tanaka
    Division of Biochemistry and Molecular Genetics, Department of Molecular and Cellular Biology, Ehime University School of Medicine, Shitsukawa, Shigenobu cho, Onsen gun, Ehime 791 0295, Japan
    J Biol Chem 279:41950-9. 2004
    ....
  35. pmc Effects of promyelocytic leukemia zinc finger protein on the proliferation of cultured human corneal endothelial cells
    Takeshi Joko
    Department of Ophthalmology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
    Mol Vis 13:649-58. 2007
    ..To determine whether the promyelocytic leukemia zinc finger (PLZF) protein, a transcriptional repressor and negative regulator during cell cycling, plays a role in the proliferation of cultured human corneal endothelial cells (HCECs)...
  36. pmc Insufficiency of pro-heparin-binding epidermal growth factor-like growth factor shedding enhances hypoxic cell death in H9c2 cardiomyoblasts via the activation of caspase-3 and c-Jun N-terminal kinase
    Teruyoshi Uetani
    Department of Biochemistry and Molecular Genetics, Center for Regenerative Medicine CEREM, Ehime University, Graduate School of Medicine, Shitsukawa, Toon, Ehime 791 0295, Japan
    J Biol Chem 284:12399-409. 2009
    ..These data indicate that insufficiency of proHB-EGF shedding under hypoxic stress leads to cardiomyocyte apoptosis via Caspase-3- and JNK-dependent pathways...
  37. ncbi request reprint [Heparin-binding EGF-like growth factor (HB-EGF)]
    Chie Morimoto
    Division of Biochemistry and Molecular Genetics, Department of Molecular and Cellular Biology, Ehime University School of Medicine
    Nihon Rinsho 63:110-2. 2005
  38. ncbi request reprint Neuroglycan C, a novel member of the neuregulin family
    Yumi Kinugasa
    Division of Biochemistry and Molecular Biology, Department of Cellular and Molecular Genetics, Ehime University School of Medicine, Shitukawa, Shigenobu cho, Onsen gun, Ehime 791 0295, Japan
    Biochem Biophys Res Commun 321:1045-9. 2004
    ..Taken together, these data indicate that NGC is an active growth factor and a direct ligand for ErbB3 and that NGC transactivates ErbB2. Thus, NGC should be classified as the sixth member (neuregulin-6) of the neuregulin family...
  39. ncbi request reprint [Membrane-anchored heparin-binding EGF-like growth factor processing by ADAM12 in cardiac hypertrophy]
    Shigeki Higashiyama
    Department of Medical Biochemistry, Ehime University School of Medicine
    Nihon Rinsho 61:767-75. 2003
    ..These data suggest that shedding of HB-EGF by ADAM12 plays an important role in cardiac hypertrophy, and that inhibition of HB-EGF shedding could be a potent therapeutic strategy for cardiac hypertrophy...
  40. doi request reprint Cisplatin influences acquisition of resistance to molecular-targeted agents through epithelial-mesenchymal transition-like changes
    Maki Kurokawa
    Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan
    Cancer Sci 104:904-11. 2013
    ....
  41. pmc The cytoplasmic tail of heparin-binding EGF-like growth factor regulates bidirectional intracellular trafficking between the plasma membrane and ER
    Miki Hieda
    Department of Biochemistry and Molecular Genetics, Graduate School of Medicine, Ehime University, Ehime 791 0295, Japan
    FEBS Open Bio 2:339-44. 2012
    ..We suggest that these anterograde and retrograde sorting signals within HB-EGF-cyto are strictly regulated by protein modification and conformation...
  42. doi request reprint Adseverin: a novel cisplatin-resistant marker in the human bladder cancer cell line HT1376 identified by quantitative proteomic analysis
    Noriyoshi Miura
    Department of Urology, Ehime University Graduate School of Medicine, Shitsukawa, Toon 791 0295, Japan
    Mol Oncol 6:311-22. 2012
    ..Our results suggest that the VDAC-SCIN interaction may inhibit mitochondria-mediated apoptosis in cisplatin-resistant cells. Targeting the VDAC-SCIN interaction may offer a new therapeutic strategy for cisplatin-resistant bladder cancer...
  43. doi request reprint ZNF689 suppresses apoptosis of hepatocellular carcinoma cells through the down-regulation of Bcl-2 family members
    Shuichiro Shigematsu
    Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan
    Exp Cell Res 317:1851-9. 2011
    ..ZNF689 may be a promising chemotherapeutic target against liver cancer...
  44. ncbi request reprint Doxycycline-dependent inducible and reversible RNA interference mediated by a single lentivirus vector
    Natsuki Matsushita
    Functional Genomics Core Laboratory, Ehime University Proteo Medicine Research Center ProMRes, Ehime, Japan
    Biosci Biotechnol Biochem 77:776-81. 2013
    ..Thus the single lentiviral vector developed in this study should be a powerful tool for doxycycline-dependent inducible and reversible RNA interference in molecular genetic studies...
  45. pmc Actin filament dynamics impacts keratinocyte stem cell maintenance
    Daisuke Nanba
    Laboratory of Stem Cell Dynamics, Ecole Polytechnique Federale de Lausanne EPFL, Lausanne, Switzerland
    EMBO Mol Med 5:640-53. 2013
    ..Importantly, continuous Rac1 inhibition in holoclones results in clonal conversion and reduction of growth potential. Together, our data connect loss of stem cells to EGF-induced colony dynamics governed by Rac1...
  46. ncbi request reprint [Epidermal growth factor (EGF)]
    Chie Morimoto
    Division of Biochemistry and Molecular Genetics, Department of Molecular and Cellular Biology, Ehime University School of Medicine
    Nihon Rinsho 63:107-9. 2005
  47. pmc Pathophysiology of lung injury induced by common bile duct ligation in mice
    Fumiaki Shikata
    Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine, Ehime, Japan
    PLoS ONE 9:e94550. 2014
    ..Our objectives were to establish a mouse model of lung injury after common bile duct ligation (CBDL) and to investigate pulmonary pathogenesis for application in future therapeutic approaches...
  48. doi request reprint Region-specific proliferative response of neural progenitors to exogenous stimulation by growth factors following ischemia
    Soichi Oya
    Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Japan
    Neuroreport 19:805-9. 2008
    ..Our results suggest that EGF and FGF-2, combined with DLL4, represent the universally applicable regimen for the expansion of the neural progenitor pool following ischemia...
  49. ncbi request reprint Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: metalloproteinase inhibitors as a new therapy
    Masanori Asakura
    Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Osaka, Japan
    Nat Med 8:35-40. 2002
    ..These data suggest that shedding of HB-EGF by ADAM12 plays an important role in cardiac hypertrophy, and that inhibition of HB-EGF shedding could be a potent therapeutic strategy for cardiac hypertrophy...
  50. pmc Heparin-binding EGF-like growth factor and ErbB signaling is essential for heart function
    Ryo Iwamoto
    Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565 0871, Japan
    Proc Natl Acad Sci U S A 100:3221-6. 2003
    ..In addition, constitutive tyrosine phosphorylation of both ErbB2 and ErbB4 was significantly reduced in HB(del/del) hearts. It was concluded that HB-EGF activation of receptor tyrosine kinases is essential for normal heart function...
  51. ncbi request reprint Gastrin enhances gastric mucosal integrity through cyclooxygenase-2 upregulation in rats
    Masato Komori
    Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2 2 Yamadaoka, Suita, Japan
    Am J Physiol Gastrointest Liver Physiol 283:G1368-78. 2002
    ..In conclusion, this study demonstrates that gastrin enhances gastric mucosal integrity through COX-2, which is partially mediated by HB-EGF, and PGE(2) upregulation in rats...
  52. ncbi request reprint Overexpression of ADAM9 in non-small cell lung cancer correlates with brain metastasis
    Yasushi Shintani
    Department of Molecular Pathology, School of Allied Health Science, Osaka University Faculty of Medicine, Suita, Japan
    Cancer Res 64:4190-6. 2004
    ....
  53. pmc Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands
    Umut Sahin
    Cell Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, Box 368, 1275 York Avenue, New York, NY 10021, USA
    J Cell Biol 164:769-79. 2004
    ..Identification of EGFR ligand sheddases is a crucial step toward understanding the mechanism underlying ectodomain release, and has implications for designing novel inhibitors of EGFR-dependent tumors...
  54. pmc Phenotypic analysis of Meltrin alpha (ADAM12)-deficient mice: involvement of Meltrin alpha in adipogenesis and myogenesis
    Tomohiro Kurisaki
    Field of Growth Regulation, Institute for Frontier Medical Sciences, Kyoto University, Japan
    Mol Cell Biol 23:55-61. 2003
    ..We also report here the chromosomal locations of Meltrin alpha in the mouse and rat...
  55. ncbi request reprint Liver regeneration in heparin-binding EGF-like growth factor transgenic mice after partial hepatectomy
    Shinichi Kiso
    Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
    Gastroenterology 124:701-7. 2003
    ..This study describes the effects of HB-EGF on liver regeneration after 70% partial hepatectomy in proHB-EGF transgenic mice with liver-specific expression. Methods &..
  56. ncbi request reprint Transactivation of epidermal growth factor receptor after heparin-binding epidermal growth factor-like growth factor shedding in the migration of prostate cancer cells promoted by bombesin
    Jun Madarame
    Department of Pathology, School of Allied Health Sciences, Faculty of Medicine, Osaka University, Osaka, Japan
    Prostate 57:187-95. 2003
    ..In this study, we tried to directly elucidate HB-EGF shedding in this pathway and to determine its contribution to the migration of prostate cancer cells...
  57. ncbi request reprint Angiopoietin-regulated recruitment of vascular smooth muscle cells by endothelial-derived heparin binding EGF-like growth factor
    Erika Iivanainen
    MediCity Research Laboratories, Department of Medical Biochemistry and Molecular Biology, University of Turku, FIN 20520 Turku, Finland
    FASEB J 17:1609-21. 2003
    ..These results suggest an important role for HB-EGF and ErbB receptors in the recruitment of SMCs by ECs and elaborate on the mechanism by which angiopoietins exert their vascular effects...
  58. ncbi request reprint PACSIN3 binds ADAM12/meltrin alpha and up-regulates ectodomain shedding of heparin-binding epidermal growth factor-like growth factor
    Seiji Mori
    Department of Molecular Pathology, School of Allied Health Science, Osaka University Faculty of Medicine, 1 7 Yamadaoka, Suita, Osaka 565 0871, USA
    J Biol Chem 278:46029-34. 2003
    ..Our data indicate that PACSIN3 has a novel function as an up-regulator in the signaling of proHB-EGF shedding induced by TPA and angiotensin II...
  59. ncbi request reprint HB-EGF is a potent inducer of tumor growth and angiogenesis
    Pat P Ongusaha
    Cancer Biology Program, Hematology and Oncology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, 4 Blackfan Circle, Boston, MA 02115, USA
    Cancer Res 64:5283-90. 2004
    ..These findings establish s-HB-EGF as a potent inducer of tumor growth and angiogenesis and suggest that therapeutic intervention aimed at the inhibition of s-HB-EGF functions may be useful in cancer treatment...
  60. ncbi request reprint The mechanism of cleavage of EGFR ligands induced by inflammatory cytokines in gastric cancer cells
    Satoshi Tanida
    Department of Internal Medicine and Bioregulation, Nagoya City University Graduate School of Medical Sciences, Mizuho, Japan
    Gastroenterology 127:559-69. 2004
    ..This study evaluated the mechanism of interleukin (IL)-8- and IL-1beta-dependent shedding of the EGFR ligand in KATO III cells...
  61. ncbi request reprint Significance of the association between heparin-binding epidermal growth factor-like growth factor and CD9 in human gastric cancer
    Yoko Murayama
    Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Yamadaoka, Suita, Osaka, Japan
    Int J Cancer 98:505-13. 2002
    ..These results indicate that the coexpression of proHB-EGF and CD9 may be involved in the tumorigenesis and/or proliferation of gastric cancers in a juxtacrine manner...
  62. ncbi request reprint Helicobacter pylori-stimulated interleukin-8 (IL-8) promotes cell proliferation through transactivation of epidermal growth factor receptor (EGFR) by disintegrin and metalloproteinase (ADAM) activation
    Takashi Joh
    Department of Internal Medicine and Bioregulation, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho cho, Mizuho ku, Nagoya, 467 8601, Japan
    Dig Dis Sci 50:2081-9. 2005
    ..This may be one of the mechanisms of hyperplastic polyp and gastric cancer development in H. pylori-infected gastric mucosa...
  63. ncbi request reprint Infiltration anesthetic lidocaine inhibits cancer cell invasion by modulating ectodomain shedding of heparin-binding epidermal growth factor-like growth factor (HB-EGF)
    Tadanori Mammoto
    Department of Anesthesiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan
    J Cell Physiol 192:351-8. 2002
    ..These data point to previously unrecognized beneficial actions of lidocaine and suggest that lidocaine might be an ideal infiltration anesthetic for surgical cancer operations...
  64. ncbi request reprint Involvement of HB-EGF and EGF receptor transactivation in TGF-beta-mediated fibronectin expression in mesangial cells
    Yoko Uchiyama-Tanaka
    Department of Medicine II, Kansai Medical University, Moriguchi, Osaka 570 8507, Japan
    Kidney Int 62:799-808. 2002
    ..Gq-coupled receptors are known to transactivate epidermal growth factor receptor (EGFR) via the Ca2+ and PKC pathways to phosphorylate extracellular signal-regulated kinase (ERK)...
  65. ncbi request reprint G protein coupling and second messenger generation are indispensable for metalloprotease-dependent, heparin-binding epidermal growth factor shedding through angiotensin II type-1 receptor
    Mizuo Mifune
    Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA
    J Biol Chem 280:26592-9. 2005
    ....
  66. ncbi request reprint IL-8 promotes cell proliferation and migration through metalloproteinase-cleavage proHB-EGF in human colon carcinoma cells
    Yusuke Itoh
    Department of Internal Medicine and Bioregulation, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho, Nagoya 467 8601, Japan
    Cytokine 29:275-82. 2005
    ....
  67. ncbi request reprint Specific molecular interactions of oversulfated chondroitin sulfate E with various heparin-binding growth factors. Implications as a physiological binding partner in the brain and other tissues
    Sarama Sathyaseelan Deepa
    Department of Biochemistry, Kobe Pharmaceutical University, Higashinada ku, Japan
    J Biol Chem 277:43707-16. 2002
    ..These findings suggest the possibility of CS-E being a binding partner, a coreceptor, or a genuine receptor for various Hep-binding growth factors in the brain and possibly also in other tissues...
  68. ncbi request reprint Roles of cell adhesion molecules in tumor angiogenesis induced by cotransplantation of cancer and endothelial cells to nude rats
    Kou Tei
    Department of Molecular Pathology, Research Institute, Aichi Cancer Center, Nagoya 464 8681, Japan
    Cancer Res 62:6289-96. 2002
    ....
  69. ncbi request reprint NF-kappaB activation in non-parenchymal liver cells after partial hepatectomy in rats: possible involvement in expression of heparin-binding epidermal growth factor-like growth factor
    Shigeru Sakuda
    Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2 2 Yamadaoka, Suita, 565 0871 Osaka, Japan
    J Hepatol 36:527-33. 2002
    ..The aims of this study were to identify NF-B-activated cells and to clarify their involvement in HB-EGF expression after PH...
  70. ncbi request reprint Activity-dependent shedding of heparin-binding EGF-like growth factor in brain neurons
    Yuji Shishido
    Division of Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata 951 8585, Japan
    Biochem Biophys Res Commun 348:963-70. 2006
    ..Therefore, we propose that glutamatergic neurotransmission in the central nervous system plays a crucial role in regulating ectodomain shedding of pro-HB-EGF...
  71. pmc Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities
    Satoru Yamazaki
    Research Institute for Microbial Diseases, Osaka University, Osaka 565 0871, Japan
    J Cell Biol 163:469-75. 2003
    ..These results indicate that ectodomain shedding of proHB-EGF is essential for HB-EGF function in vivo, and that this process requires strict control...
  72. ncbi request reprint Osteoactivin fragments produced by ectodomain shedding induce MMP-3 expression via ERK pathway in mouse NIH-3T3 fibroblasts
    Harumi Furochi
    Department of Nutritional Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
    FEBS Lett 581:5743-50. 2007
    ..Our results suggest that the extracellular fragments of osteoactivin produced by shedding act as a growth factor to induce MMP-3 expression via the ERK pathway in fibroblasts...
  73. ncbi request reprint The HNF-1 target collectrin controls insulin exocytosis by SNARE complex formation
    Kenji Fukui
    Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita Osaka 565 0871, Japan
    Cell Metab 2:373-84. 2005
    ..Therefore, collectrin is a regulator of SNARE complex function, which thereby controls insulin exocytosis...
  74. doi request reprint The tetraspanin CD9 modulates epidermal growth factor receptor signaling in cancer cells
    Yoko Murayama
    Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Suita, Japan
    J Cell Physiol 216:135-43. 2008
    ..These results suggest that CD9 might have an important role that attenuates EGFR signaling. Therefore, CD9 not only associates EGFR but also a new regulator, which may affect EGF-induced signaling in cancer cells...
  75. ncbi request reprint Regenerative and therapeutic effects of heparin-binding epidermal growth factor-like growth factor on diabetes by gene transduction through retrograde pancreatic duct injection of adenovirus vector
    Junji Kozawa
    Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan
    Pancreas 31:32-42. 2005
    ..A member of the epidermal growth factor (EGF) family, heparin binding (HB)-EGF, may promote this process. We examined whether HB-EGF gene transduction into duct cells could promote beta-cell regeneration...
  76. ncbi request reprint Structure-based virtual screening and biological evaluation of potent and selective ADAM12 inhibitors
    Myungsok Oh
    Department of Life Science and National Research Laboratory of Proteolysis, Gwangju Institute of Science and Technology, 1 Oryong dong, Buk Gu, Gwangju 500 712, Republic of Korea
    Bioorg Med Chem Lett 14:6071-4. 2004
    ..The mechanism underlying the potency and selectivity of a representative compound, 5, was investigated through molecular docking studies...
  77. ncbi request reprint CD9-mediated activation of the p46 Shc isoform leads to apoptosis in cancer cells
    Yoko Murayama
    Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2 2 B5, Yamadaoka, Suita 565 0871, Japan
    J Cell Sci 117:3379-88. 2004
    ..These results suggest that CD9 might regulate apoptosis through the specialized signals in human cancer cell lines...
  78. pmc Distinct mechanisms of receptor and nonreceptor tyrosine kinase activation by reactive oxygen species in vascular smooth muscle cells: role of metalloprotease and protein kinase C-delta
    Gerald D Frank
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Mol Cell Biol 23:1581-9. 2003
    ....
  79. ncbi request reprint The N-terminal region of NTAK/neuregulin-2 isoforms has an inhibitory activity on angiogenesis
    Norihiko Nakano
    Department of Molecular Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo cho, Izumi, Osaka 594 1101, Japan
    J Biol Chem 279:11465-70. 2004
    ..These results suggest that the active site of NTAK is localized outside of the EGF-like domain but within the N-terminal region, including the Ig-like domain, of NTAK...
  80. ncbi request reprint Identification and characterization of novel mouse and human ADAM33s with potential metalloprotease activity
    Tsuyoshi Yoshinaka
    R and D Laboratories, Nippon Organon K K, 1 5 90 Tomobuchi cho, Miyakojima, Osaka 534 0016, Japan
    Gene 282:227-36. 2002
    ..From the results of phylogenic analysis based on primary amino acid sequence and distribution of the mRNA, these novel ADAM genes were thus named ADAM33...