A Chimera between Platelet-Derived Growth Factor β-Receptor and Fibroblast Growth Factor Receptor-1 Stimulates Pancreatic β-Cell. DNA Synthesis in the Presence of PDGF-BB

Abstract

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) β-receptor (PDGFR-β) 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-β, the FGFR-1 and the chimera between PDGFR-β 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-β or the chimeric PDGFR-β/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-β or PDGFR-β/FGFR-1. Cotransfection of the PDGFR-β and the chimeric PDGFR-β/FGFR-1 constructs attenuated the stimulation of DNA synthesis in response to PDGF-BB. Receptor binding studies showed binding with a K_d of 0.7 nM to the chimeric receptor. The present findings show that when the chimeric PDGFR-β/FGFR-1 construct is expressed in β-cells it is efficient in increasing DNA synthesis when stimulated with ligand.

Key Words:

• islets
• chimeric receptor
• DNA synthesis