A chimera between platelet-derived growth factor beta-receptor and fibroblast growth factor receptor-1 stimulates pancreatic beta-cell DNA synthesis in the presence of PDGF-BB.
This study was undertaken to characterize the expression of a chimeric growth factor receptor composed of the extracellular and transmembrane domains of the platelet-derived growth factor (PDGF) beta-receptor (PDGFR-beta) fused to the intracellular domain of the fibroblast growth factor receptor-1 (FGFR-1) and to assess its effect on the growth potential of pancreatic islet cells. For this purpose rat pancreatic islets or monolayers of pancreatic islet cells were transfected with recombinant DNA constructs coding for the PDGF B-chain, the PDGFR-beta, the FGFR-1 and the chimera between PDGFR-beta and FGFR-1. DNA synthesis, monitored as the percentage of labelled nuclei and [3H]thymidine incorporation, was stimulated in pancreatic islet cells cotransfected with the constructs coding for the PDGF B-chain and the PDGFR-beta or the chimeric PDGFR-beta/FGFR-1 as compared with that determined after transfection with control plasmid. PDGF-BB stimulated DNA synthesis when islet cells had been transfected with PDGFR-beta or PDGFR-beta/FGFR-1. Cotransfection of the PDGFR-beta and the chimeric PDGFR-beta/FGFR-1 constructs attenuated the stimulation of DNA synthesis in response to PDGF-BB. Receptor binding studies showed binding with a Kd of 0.7 nM to the chimeric receptor. The present findings show that when the chimeric PDGFR-beta/FGFR-1 construct is expressed in beta-cells it is efficient in increasing DNA synthesis when stimulated with ligand.
Mares
J
J
Department of Medical Cell Biology, Uppsala University, Sweden.
Claesson-Welsh
L
L
Welsh
M
M
D000818:Animals; D002678:Chimera; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects; D005260:Female; D005312:Fetal Blood; D005346:Fibroblast Growth Factors / Q000235:genetics; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008940:Mitotic Index; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D017468:Receptors, Fibroblast Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor; D011994:Recombinant Proteins / Q000187:drug effects / Q000502:physiology; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014162:Transfection
D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D012710:Serum Albumin, Bovine; D005346:Fibroblast Growth Factors; D004247:DNA; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor