A NATURAL KINASE-DEFICIENT VARIANT OF FIBROBLAST GROWTH-FACTOR RECEPTOR-1

A fibroblast growth factor receptor 1 variant missing 37 amino acids f rom the carboxy-terminal tyrosine kinase catalytic domain was discover ed in human lung fibroblasts and several other human cell lines. The r eceptor variant binds specifically to acidic fibroblast growth factor but has no tyrosine kinase activity. It was found that cellular transf ectants expressing the fibroblast growth factor receptor 1 variant are mitogenically inactive and ligand binding to the receptor causes neit her receptor autophosphorylation nor phospholipase C-gamma transphosph orylation. The fibroblast growth factor receptor I variant therefore r epresents an inactive receptor for acidic fibroblast growth factor. Si nce both kinase and kinase-deficient receptor forms are expressed in c ells, it is conceivable that the kinase-deficient receptor plays an im portant role in regulating cellular responses elicited by acidic fibro blast growth factor stimulation.