A truncated form of fibroblast growth factor receptor 1 inhibits signal transduction by multiple types of fibroblast growth factor receptor.
A truncated form of the type 1 fibroblast growth factor receptor (FGFR1) lacking most of its cytoplasmic domain was tested for its ability to inhibit signal transduction by each of three different wild-type FGFRs (FGFR1, 2, and 3). When the truncated FGFR1 was expressed in Xenopus oocytes in excess of each wild-type FGFR, mobilization of intracellular calcium mediated by the wild-type FGFRs was completely blocked. The truncated FGFR did not inhibit signal transduction by the co-expressed platelet-derived growth factor beta-receptor. A form of truncated FGFR1 which lacked the first immunoglobulin-like domain also inhibited signal transduction by wild-type FGFRs. Truncated FGFR formed complexes with wild-type FGFR in the presence of basic FGF in intact cells. These observations were consistent with the hypothesis that the truncated FGFR interacted with wild-type FGFRs to form nonfunctional heterodimers, thus eliminating the signaling by the wild-type FGFRs. The observation that signaling by multiple types of FGFR can be blocked by a single type of truncated FGFR suggests that the different types of FGFR can interact with each other in ligand-mediated complexes. These findings provide a molecular basis for inhibiting the actions of FGFs in vivo.
Ueno
H
H
Department of Medicine, University of California, San Francisco 94143-0724.
Gunn
M
M
Dell
K
K
Tseng
A
A
Williams
L
L
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002645:Chickens; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D017468:Receptors, Fibroblast Growth Factor; D015183:Restriction Mapping; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic; D029867:Xenopus Proteins; D014982:Xenopus laevis
D046911:Macromolecular Substances; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D029867:Xenopus Proteins; D016222:Fibroblast Growth Factor 2; C496353:FGFR2 protein, human; C496357:Fgfr2 protein, Xenopus; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D002118:Calcium