title: Ligand dependent and independent internalization and nuclear translocation of fibroblast growth factor (FGF) receptor 1.
abstract: Basic fibroblast growth factor (FGF-2) is one of the prototype members of a rapidly expanding family of polypeptides. FGF-2 acts on cells via a dual-receptor system consisting of high-affinity tyrosine kinase receptors (FGFR) and low-affinity receptors comprised of heparan sulfate proteoglycans. Following ligand binding and subsequent internalization, both FGF-2 and FGFR1 are translocated to the nucleus where they have activities distinct from those expressed at the cell surface. Despite the growing number of growth factors and receptors shown to translocate to the nucleus, little is known about the mechanisms of internalization and translocation and how these processes are regulated. In the studies reported in this paper, we examined the roles of clathrin-dependent and -independent endocytosis in the uptake of FGFR1 and one of its ligands, FGF-2. While the uptake of FGF-2 occurred at least partly by a caveolar-dependent mechanism, that of FGFR1 was independent of both caveolae and coated pits. Surprisingly, neither the uptake of FGF-2 nor FGFR1 required the activity of the receptor tyrosine kinase. In addition, we identified a cell cycle-dependent pathway of FGFR1 nuclear translocation that appears to be independent of ligand binding.
authors.affiliation: Department of Cell Biology, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Reilly
authors.forename: Eiichi
authors.initials: E
authors.lastname: Mizukoshi
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Maher
mesh_terms: D016475:3T3 Cells; D000818:Animals; D021941:Caveolae / Q000502:physiology; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D002966:Clathrin / Q000494:pharmacology; D004705:Endocytosis; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D008024:Ligands; D051379:Mice; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D011994:Recombinant Proteins; D015398:Signal Transduction
chemical_list: D002966:Clathrin; D008024:Ligands; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; C496349:Fgfr1 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1