title: Neurotropin promotes NGF signaling through interaction of GM1 ganglioside with Trk neurotrophin receptor in PC12 cells.
abstract: Activation of the high-affinity nerve growth factor (NGF) receptor Trk occurs through multiple processes consisted of translocation and clustering within the plasma membrane lipid rafts, dimerization and autophosphorylation. Here we found that a nonprotein extract of inflamed rabbit skin inoculated with vaccinia virus (Neurotropin(®)) enhanced efficiency of NGF signaling. In rat pheochromocytoma PC12 cells overexpressing Trk (PCtrk cells), Neurotropin augmented insufficient neurite outgrowth observed at suboptimal concentration of NGF (2ng/mL) in a manner depending on Trk kinase activity. Cellular exposure to Neurotropin resulted in an accumulation of Trk-GM1 complexes without affecting dimerization or phosphorylation states of Trk. Following NGF stimulation, Neurotropin significantly facilitated the time course of NGF-induced Trk autophosphorylation. These observations provide a unique mechanism controlling efficiency of NGF signaling, and raise the therapeutic potential of Neurotropin for various neurological conditions associated with neurotrophin dysfunction.
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan; Division of Pulmonary and Critical Care Medicine, Allergy and Clinical Immunology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA; Nippon-Zoki Pharmaceutical Co., Ltd., Osaka 564-0052, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Fukuda
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Fukui
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Hikichi
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
authors.forename: Tomomasa
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Murate
authors.affiliation: Nippon-Zoki Pharmaceutical Co., Ltd., Osaka 564-0052, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Adachi
authors.affiliation: Nippon-Zoki Pharmaceutical Co., Ltd., Osaka 564-0052, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Imai
authors.affiliation: The National Institute of Nursing Research, National Institutes of Health, Bethesda, MD 20892, USA; Nippon-Zoki Pharmaceutical Co., Ltd., Osaka 564-0052, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Fukuhara
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ueda
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Allergy and Clinical Immunology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Allen P
authors.initials: AP
authors.lastname: Kaplan
authors.affiliation: Department of Neurology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan. Electronic address: tmutoh@fujita-hu.ac.jp.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Mutoh
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D005677:G(M1) Ganglioside / Q000378:metabolism*; D026121:Indole Alkaloids / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects; D016716:PC12 Cells; D011134:Polysaccharides / Q000494:pharmacology*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000700:Analgesics; D002227:Carbazoles; D026121:Indole Alkaloids; D011134:Polysaccharides; D005677:G(M1) Ganglioside; C010491:neurotropin; D020932:Nerve Growth Factor; C049985:staurosporine aglycone; D020794:Receptor Protein-Tyrosine Kinases
keywords: GM1 ganglioside; NGF signaling; Neurotropin; Trk tyrosine kinase