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Normal Human Fibroblasts Produce Membrane-Bound and Soluble Isoforms of FGFR-1
Institution:1. Legacy Clinical Research and Technology Center, P.O. Box 3950, Portland, Oregon, 97208-3950;2. Cascade Biologics, Inc. 4475 SW Scholls Ferry Road, No. 101, Portland, Oregon, 97225;1. Department of Radiation Oncology, Hospital Universitari Sant Joan, Institut d’Investigació Sanitària Pere i Virgili, Universitat Rovira i Virgili, Reus, Spain;2. Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d’Investigació Sanitària Pere i Virgili, Universitat Rovira i Virgili, Reus, Spain;3. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran;4. Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;5. Department of Radiation Oncology, Complejo Hospitalario Universitario de Albacete, Albacete, Spain;6. Department of Pathology, Hospital Universitari Sant Joan, Institut d’Investigació Sanitària Pere i Virgili, Universitat Rovira i Virgili, Reus, Spain;1. Department of Molecular Medicine, Lipid Clinic and Atherosclerosis Prevention Centre, ‘Umberto I’ Hospital - ‘Sapienza’ University of Rome, Rome, Italy;2. Department of Internal Medicine - Polyclinic Hospital San Martino, University of Genoa, Genoa, Italy;3. Department of Food and Drug, University of Parma, Parma, Italy;4. Endocrinology and Metabolic Diseases, Civile Maggiore Hospital of Verona, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy;5. Immunohematology and Transfusion Medicine, ASL3, Pistoia, Italy;6. Department of Internal Medicine, University of Genoa, Italy;7. Department of Life Sciences, University of Parma, Italy;8. Inserm UMR_S1140 “Innovative Therapies in Haemostasis” Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, France;9. French Institute of Health and Medical Research (Inserm), France;10. Department of Medicine, Northwest Lipid Research Laboratories, University of Washington, Seattle, WA, USA;11. School of Medicine, Faculty of Health and Medical Sciences - Cardiometabolic Service, Department of Cardiology, Royal Perth Hospital University of Western Australia, Perth, Western Australia, Australia;1. School of Chemistry and Chemical Engineering, Jiangsu Normal University, Xuzhou 221116, PR China;2. Key Laboratory of Biotechnology on Medical Plant of Jiangsu Province, Jiangsu Normal University, Xuzhou 221116, PR China
Abstract:Fibroblast growth factors (FGFs) are polypeptide mitogens for a wide variety of cell types and are involved in other processes such as angiogenesis and cell differentiation. FGFs mediate their biological responses by activating high-affinity tyrosine kinase receptors. Currently, there are four human fibroblast growth factor receptor (FGFR) genes. To investigate the mechanisms by which αFGF and βFGF may mediate mitogenic signal transduction in human skin-derived fibroblasts, we analyzed these cells for the presence of high-affinity FGFRs. We show that normal human dermal fibroblasts express a single high-affinity FGFR gene, FGFR-1. Cloning and sequencing of two distinct FGFR-1 cDNAs suggested that normal human dermal fibroblasts express a membrane-bound and a putatively secreted form of FGFR-1. We show that normal human dermal fibroblasts produce two FGFR-1 proteins, one of which exists in conditioned media. The mRNA for the putatively secreted form of FGFR-1 appears to be down-regulated by serum treatment of the cells.
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