Decorin is a biological ligand for the epidermal growth factor receptor
Decorin is a biological ligand for the epidermal growth factor receptor
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DOI：
10.1074/jbc.274.8.4489
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发表时间：
1999-02-19
影响因子：
4.8
通讯作者：
Eichstetter, I
中科院分区：
文献类型：
--
作者：
Iozzo, RV;Moscatello, DK;Eichstetter, I
核心蛋白聚糖的异位表达在具有不同组织发生学背景的转化细胞中诱导深刻的细胞抑制作用。其作用机制最近才开始阐明。外源性核心蛋白聚糖激活表皮生长因子（EGF）受体，从而触发信号级联反应，导致促分裂原活化蛋白（MAP）激酶磷酸化，诱导p21和生长抑制。在这项研究中，我们证明了核心蛋白聚糖与EGF受体的直接相互作用。核心蛋白聚糖的结合诱导鳞状细胞癌细胞中EGF受体的二聚化和MAP激酶的快速持续磷酸化。在无细胞系统中，核心蛋白聚糖通过激活受体酪氨酸激酶诱导纯化的EGF受体的自磷酸化，并且还可以作为EGF受体激酶本身的底物。使用放射性配体结合试验，我们表明，固定化和可溶性核心蛋白聚糖结合到EGF受体胞外域或纯化的EGF受体。结合由蛋白质核心介导，并且具有相对低的亲和力（K-d类似于87 nM）。因此，核心蛋白聚糖应该被认为是EGF受体的一种新的生物配体，这种相互作用可以在重塑和癌症生长过程中调节细胞生长。
Ectopic expression of decorin induces profound cytostatic effects in transformed cells with diverse histogenetic backgrounds. The mechanism of action has only recently begun to be elucidated. Exogenous decorin activates the epidermal growth factor (EGF) receptor, thereby triggering a signaling cascade that leads to phosphorylation of mitogen-activated protein (MAP) kinase, induction of p21, and growth suppression. In this study we demonstrate a direct interaction of decorin with the EGF receptor. Binding of decorin induces dimerization of the EGF receptor and rapid and sustained phosphorylation of MAP kinase in squamous carcinoma cells. In a cell-free system, decorin induces autophosphorylation of purified EGF receptor by activating the receptor tyrosine kinase and can also act as a substrate for the EGF receptor kinase itself. Using radioligand binding assays we show that both immobilized and soluble decorin bind to the EGF receptor ectodomain or to purified EGF receptor. The binding is mediated by the protein core and has relatively low affinity (K-d similar to 87 nM). Thus, decorin should be considered as a novel biological ligand for the EGF receptor, an interaction that could regulate cell growth during remodeling and cancer growth.