EXPRESSION OF 2 DIFFERENT FORMS OF FIBROBLAST GROWTH-FACTOR RECEPTOR-1 IN DIFFERENT MOUSE-TISSUES AND CELL-LINES
EXPRESSION OF 2 DIFFERENT FORMS OF FIBROBLAST GROWTH-FACTOR RECEPTOR-1 IN DIFFERENT MOUSE-TISSUES AND CELL-LINES
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DOI：
10.1073/pnas.88.17.7625
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发表时间：
1991-09-01
影响因子：
11.1
通讯作者：
REID, HH
中科院分区：
文献类型：
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作者：
BERNARD, O;LI, M;REID, HH
成纤维细胞生长因子受体 (FGFR) 形成一个至少有四个成员的多基因家族，所有成员均具有由两个或三个免疫球蛋白样（Ig 样）结构域组成的胞外区域。通过 RNase 保护分析，我们分析了各种组织和细胞系中 FGFR-1 mRNA 的表达，并证明所有研究的细胞系都以相似的水平表达至少两种不同形式的 FGFR-1。尽管肌肉和心脏表达具有两个 [FGFR-1 短 (FGFR-1S)] 或三个 [FGFR-1 长 (FGFR-1L)] Ig 样结构域的形式，但发育中的大脑和成人大脑仅表达编码较长形式的 mRNA。通过将表达它们的表达载体稳定引入Rat-2成纤维细胞和FDC-P1骨髓细胞中，进一步表征了这两种形式的受体。用酸性 FGF (aFGF) 或碱性 FGF (bFGF) 处理转染的 Rat-2 细胞导致病灶形成。在培养物中生长> 2个月后，即使不添加配体，也观察到转化的表型。 I-125 标记的 bFGF (I-125-bFGF) 与表达 FGFR-1L 或 FGFR-1S 的 Rat-2 细胞交联，产生两种相似的 150 和 110 kDa 复合物。尽管表达 FGFR-1L 的 Rat-2 细胞与 I-125 标记的 aFGF (I-125-aFGF) 产生相似的复合物，但与表达 FGFR-1S 的细胞仅形成 150 kDa 复合物。当 I-125-aFGF 或 I-125-bFGF 与表达 FGFR-1L 的 FDC-P1 细胞交联时，也观察到 150-kDa 复合物。值得注意的是，只有当交联反应中存在肝素时才能观察到这些复合物。表达 FGFR-1 的 FDC-P1 细胞以高亲和力结合 aFGF 和 bFGF，但仅在肝素存在的情况下。在肝素存在的情况下，这些细胞的因子依赖性可以从白细胞介素3转变为FGF。
The fibroblast growth factor receptors (FGFRs) form a multigene family of at least four members, all having extracellular regions consisting of either two or three immunoglobulin-like (Ig-like) domains. By RNase protection analysis we have analyzed the expression of FGFR-1 mRNA in various tissues and cell lines and demonstrated that all of the cell lines studied expressed at least two different forms of the FGFR-1 at similar levels. Although muscle and heart express forms having either two [FGFR-1 short (FGFR-1S)] or three [FGFR-1 long (FGFR-1L)] Ig-like domains, the developing brain and adult brain express only mRNA encoding the longer form. The two forms of the receptor were characterized further by stably introducing expression vectors expressing them into Rat-2 fibroblasts and FDC-P1 myeloid cells. Treatment of the transfected Rat-2 cells with acidic FGF (aFGF) or basic FGF (bFGF) resulted in focus formation. The transformed phenotype was observed even without addition of ligand after growth in culture for > 2 months. Cross-linking of I-125-labeled bFGF (I-125-bFGF) to Rat-2 cells expressing either FGFR-1L or FGFR-1S yielded two similar complexes of 150 and 110 kDa. Although Rat-2 cells expressing FGFR-1L yielded similar complexes with I-125-labeled aFGF (I-125-aFGF), only the 150-kDa complex was formed with cells expressing FGFR-1S. The 150-kDa complex was also observed when I-125-aFGF or I-125-bFGF was cross-linked to FDC-P1 cells expressing FGFR-1L. Significantly, these complexes were only observed when heparin was present in the cross-linking reaction. FDC-P1 cells expressing FGFR-1 bound aFGF and bFGF with high affinity but only in the presence of heparin. The factor dependence of these cells could be switched from interleukin 3 to FGF in the presence of heparin.