Santos-Ocampo S, Colvin J S, Chellaiah A, Ornitz D M
Department of Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, Missouri 63110, USA.
J Biol Chem. 1996 Jan 19;271(3):1726-31. doi: 10.1074/jbc.271.3.1726.
Receptor specificity is an essential mechanism governing the activity of fibroblast growth factors (FGF). To begin to understand the developmental role of FGF-9/glial activating factor, we have cloned and sequenced the murine FGF-9 cDNA and expressed the protein in mammalian cells and in Escherichia coli. We demonstrate that the FGF-9 protein is highly conserved between mouse and human. Receptor specificity was determined by direct binding to soluble and cell surface forms of FGF receptor (FGFR) splice variants and by the mitogenic activity on cells, which express unique FGF receptor splice variants. Our data demonstrate that FGF-9 efficiently activates the "c" splice forms of FGFR2 and FGFR3, receptors expressed in potential target cells for FGF-9. Significantly, FGF-9 also binds to and activates the "b" splice form of FGFR3, thus becoming the first FGF ligand besides FGF-1 to activate this highly specific member of the FGF receptor family.
受体特异性是控制成纤维细胞生长因子（FGF）活性的一种重要机制。为了开始了解FGF-9/神经胶质激活因子在发育中的作用，我们克隆并测序了小鼠FGF-9 cDNA，并在哺乳动物细胞和大肠杆菌中表达了该蛋白。我们证明FGF-9蛋白在小鼠和人类之间高度保守。通过直接结合FGF受体（FGFR）剪接变体的可溶性和细胞表面形式以及对表达独特FGF受体剪接变体的细胞的促有丝分裂活性来确定受体特异性。我们的数据表明，FGF-9有效地激活FGFR2和FGFR3的“c”剪接形式，这些受体在FGF-9的潜在靶细胞中表达。重要的是，FGF-9还结合并激活FGFR3的“b”剪接形式，从而成为除FGF-1之外第一个激活FGF受体家族这一高度特异性成员的FGF配体。
