Heparan sulfate proteoglycan and FGF receptor target basic FGF to different intracellular destinations.
Heparan sulfate proteoglycan and FGF receptor target basic FGF to different intracellular destinations.
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发表时间：
1993-08
影响因子：
4
通讯作者：
Jane Reiland;A. Rapraeger
中科院分区：
文献类型：
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作者：
Jane Reiland;A. Rapraeger
碱性 FGF 是肝素结合生长因子家族的原型，可调节多种细胞反应，包括细胞生长、形态发生和分化。至少有两个受体家族结合 bFGF 并可介导其反应：(1) 含有酪氨酸激酶的 FGF 受体，称为 FGFR-1 至 FGFR-4，以及 (2) 硫酸乙酰肝素蛋白聚糖，通过其硫酸乙酰肝素链结合 bFGF。已知两者都会经历内化，因此与不同受体结合的 bFGF 可能通过不止一种途径内化。目前尚不清楚 bFGF 的细胞内命运是否因细胞表面与其结合的受体而异。为了研究这些受体在 bFGF 细胞内靶向中各自的作用，我们利用 NMuMG 细胞，该细胞通过其硫酸乙酰肝素蛋白聚糖结合和内化 bFGF，但不表达可检测水平的 FGFR，也不对 bFGF 做出反应。使用与皂素 (bFGF-皂素) 缀合的碱性 FGF 作为探针来研究不同受体对 bFGF 的靶向作用。皂草素是一种细胞毒素，外源添加对细胞没有影响。然而，如果它进入细胞质，就会杀死细胞。 NMuMG 细胞内化 bFGF-皂素，但不会被杀死。用 FGFR-1 转染这些细胞会产生 bFGF 反应性细胞，这些细胞通过 FGFR-1 结合并内化 bFGF，然后被杀死。从这些细胞中去除硫酸乙酰肝素可以消除 bFGF-皂素的杀伤作用。（摘要截断为 250 字）
Basic FGF is a prototype of a family of heparin binding growth factors that regulate a variety of cellular responses including cell growth, morphogenesis and differentiation. At least two families of receptors bind bFGF and could mediate its response: (1) tyrosine kinase-containing FGF receptors, designated FGFR-1 to FGFR-4, and (2) heparan sulfate proteoglycans that bind bFGF through their heparan sulfate chains. Both are known to undergo internalization and thus bFGF bound to the different receptors may be internalized via more than one pathway. It is not known whether the intracellular fate of bFGF differs depending upon which receptor binds it at the cell surface. To investigate the respective roles of these receptors in the intracellular targeting of bFGF, we utilized NMuMG cells that bind and internalize bFGF through their heparan sulfate proteoglycans, but do not express detectable levels of FGFRs nor respond to bFGF. Basic FGF conjugated to saporin (bFGF-saporin) was used as a probe to study targeting of bFGF by the different receptors. Saporin is a cytotoxin that has no effect on cells if added exogenously. However, it kills cells if it gains access to the cytoplasm. The NMuMG cells internalize bFGF-saporin but are not killed. Transfecting these cells with FGFR-1 results in bFGF-responsive cells, which bind and internalize bFGF through FGFR-1, and are killed. Removing the heparan sulfate from these cells eliminates killing by bFGF-saporin.(ABSTRACT TRUNCATED AT 250 WORDS)