| Abstract
| - Keratinocyte growth factor (KGF) is an unusual fibroblast growth factor (FGF) family memberin that its activity is largely restricted to epithelial cells, and added heparin/heparan sulfate inhibits itsactivity in most cell types. The effects of heparan sulfate proteoglycan (HSPG) on binding and signalingby acidic FGF (aFGF) and KGF via the KGFR were studied using surface-bound and soluble receptorisoforms expressed in wild type and mutant Chinese hamster ovary (CHO) cells lacking HSPG. Lowconcentrations of added heparin (1 μg/mL) enhanced the affinity of ligand binding to surface-bound KGFRin CHO mutants, as well as ligand-stimulated MAP kinase activation and c-fos induction, but had littleeffect on binding or signaling in wild type CHO cells. Higher heparin concentrations inhibited KGF, butnot aFGF, binding and signaling. In addition to the known interaction between HSPG and KGF, wefound that the KGFR also bound heparin. The biphasic effect of heparin on KGF, but not aFGF, bindingand signaling suggests that occupancy of the HSPG binding site on the KGFR may specifically inhibitKGF signaling. In contrast to events on the cell surface, added heparin was not required for high-affinitysoluble KGF−KGFR interaction. These results suggest that high-affinity ligand binding is an intrinsicproperty of the receptor, and that the difference between the HSPG-dependent ligand binding to receptoron cell surfaces and the HSPG-independent binding to soluble receptor may be due to other molecule(s)present on cell surfaces.
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