title: A mechanism of cell survival: sequestration of Fas by the HGF receptor Met.
abstract: Death receptors such as Fas are present in a variety of organs including liver and play an important role in homeostasis. What prevents these harmful receptors from forming homooligomers, clustering, and initiating the apoptotic pathway is not known. Here, we report the discovery of a cell survival mechanism by which Met, a growth factor receptor tyrosine kinase, directly binds to and sequesters the death receptor Fas in hepatocytes. This interaction prevents Fas self-aggregation and Fas ligand binding, thus inhibiting Fas activation and apoptosis. Our results describe a direct link between growth factor tyrosine kinase receptors and death receptors to establish a novel paradigm in growth regulation.
authors.affiliation: Department of Pathology, Division of Cellular and Molecular Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.forename: Marie C
authors.initials: MC
authors.lastname: DeFrances
authors.forename: Yu
authors.initials: Y
authors.lastname: Dai
authors.forename: Peter
authors.initials: P
authors.lastname: Pediaditakis
authors.forename: Carla
authors.initials: C
authors.lastname: Johnson
authors.forename: Aaron
authors.initials: A
authors.lastname: Bell
authors.forename: George K
authors.initials: GK
authors.lastname: Michalopoulos
authors.forename: Reza
authors.initials: R
authors.lastname: Zarnegar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D029681:Arabidopsis Proteins; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000502:physiology; D002470:Cell Survival / Q000502:physiology*; D016895:Culture Media, Serum-Free; D053222:Fas Ligand Protein; D044943:Fatty Acid Desaturases / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D010766:Phosphorylation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D019859:Proto-Oncogene Proteins c-met / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D029681:Arabidopsis Proteins; D016895:Culture Media, Serum-Free; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D019014:fas Receptor; D017228:Hepatocyte Growth Factor; D044943:Fatty Acid Desaturases; C084083:Fad7 protein, Arabidopsis; D019859:Proto-Oncogene Proteins c-met; C505530:CASP8 protein, human; C506433:CASP9 protein, human; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases