Proceedings of the National Academy of Sciences · 1990 · 194 citations · 19 references
Life SciencesCell BiologyMolecular BiologyCell ProliferationCell SignalingSignal TransductionGrowth Factor SignalingMitogenic SignalingReceptor Tyrosine Kinase SignalingExpression Vector CloningFibroblast Growth Factor Receptor SignalingGrowth Factor Receptor ActivationGrowth FactorsImmunoglobulin DomainsImmunoglobulin-like DomainsReceptor Tyrosine Kinase ActivationTyrosine Kinase Receptors
We have cloned a murine cDNA encoding a tyrosine kinase receptor with about 90% similarity to the chicken fibroblast growth factor (FGF) receptor and the human fms-like gene (FLG) tyrosine kinase. This mouse receptor lacks 88 amino acids in the extracellular portion, leaving only two immunoglobulin-like domains compared to three in the chicken FGF receptor. The cDNA was cloned into an expression vector and transfected into receptor-negative CHO cells. We show that cells expressing the receptor can bind both basic FGF and Kaposi FGF. Although the receptor binds basic FGF with a 15- to 20-fold higher affinity, Kaposi FGF is able to induce down-regulation of the receptor to the same extent as basic FGF. The receptor is phosphorylated upon stimulation with both FGFs, DNA synthesis is stimulated, and a proliferative response is produced in cells expressing the receptor, whereas cells expressing the cDNA in the antisense orientation show none of these responses to basic FGF or Kaposi FGF. Thus this receptor can functionally interact with two growth factors of the FGF family.
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