Different abilities of the four FGFRs to mediate FGF-1 translocation are linked to differences in the receptor
Vigdis Sørensen1, Antoni Wiedlocha, Ellen Margrethe Haugsten
1The Department of Biochemistry, Institute for Cancer Research, The University of Oslo, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway. vigdis.sorensen@labmed.uio.no
Abstract:
Members of the fibroblast growth factor family bind to one or more of the four closely related membrane-spanning FGF receptors. In addition to signaling through the receptors, exogenous FGF-1 and FGF-2 are endocytosed and translocated to the cytosol and nucleus where they stimulate RNA and DNA synthesis. Here we have studied the ability of the four FGF receptors to facilitate translocation of exogenous FGF-1 to the cytosol and nucleus. FGFR1 and FGFR4 were able to mediate translocation, whereas FGFR2 and FGFR3 completely lacked this ability. By analyzing mutant FGFRs we found that the tyrosine kinase domain could be deleted from FGFR1 without abolishing translocation, whereas the C-terminal tail of the FGFRs, constituted by approximately 50 amino acids downstream of the kinase domain, plays a crucial role in FGF-1 translocation. Three amino acids residues within the C-terminal tail were found to be of particular importance for translocation. For FGFR2, the two amino acid substitutions Q774M and P800H were sufficient to enable the receptor to support FGF-1 translocation. The results demonstrate a striking diversity in function of the four FGFRs determined by their C-terminal domain.
More Related Videos
10:00An Analytical Tool that Quantifies Cellular Morphology Changes from Three-dimensional Fluorescence Images
Published on: August 31, 2012
07:32Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library
Published on: September 30, 2019
Related Concept Videos
Transducer Mechanism: G Protein–Coupled Receptors
GPCRs are also called heptahelical, 7TM, or...
G Protein-coupled Receptors
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Intracellular Signaling Affects Focal Adhesions
Some...
Enzyme-linked Receptors
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
TGF - β Signaling Pathway
Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
