Mansukhani A, Moscatelli D, Talarico D, Levytska V, Basilico C
Department of Microbiology, New York University School of Medicine, NY 10016.
Proc Natl Acad Sci U S A. 1990 Jun;87(11):4378-82. doi: 10.1073/pnas.87.11.4378.
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.
我们克隆了一个小鼠cDNA,它编码一种酪氨酸激酶受体,与鸡成纤维细胞生长因子(FGF)受体和人类fms样基因(FLG)酪氨酸激酶有大约90%的相似性。这种小鼠受体在细胞外部分缺少88个氨基酸,与鸡FGF受体的三个免疫球蛋白样结构域相比,只剩下两个。将该cDNA克隆到表达载体中,并转染到受体阴性的CHO细胞中。我们发现表达该受体的细胞能够结合碱性FGF和卡波西FGF。尽管该受体与碱性FGF结合的亲和力高15至20倍,但卡波西FGF能够与碱性FGF一样程度地诱导受体下调。用两种FGF刺激后,该受体都会被磷酸化,DNA合成受到刺激,表达该受体的细胞会产生增殖反应,而以反义方向表达cDNA的细胞对碱性FGF或卡波西FGF均无这些反应。因此,该受体可与FGF家族的两种生长因子发生功能性相互作用。