A src-related kinase in the brush border membranes of gastrointestinal cells is regulated by c-met.

A src-related kinase in the brush border membranes of gastrointestinal cells is regulated by c-met.
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胃肠道细胞刷状缘膜中的 src 相关激酶受 c-met 调节。

DOI:
10.1006/excr.1999.4550
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发表时间:
1999
期刊:
Experimental cell research.
影响因子:
--
通讯作者:
Avigan,M
Avigan,M
中科院分区:
--
文献类型:
--
作者:
Sunitha,I;Shen,R;McKillop,IH;Lee,JH;Resau,J;Avigan,M

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肝细胞生长因子(HGF)通过与PTK跨膜受体c-met结合来激发多效性细胞反应。最近在进入肠腔的液体中鉴定出HGF,这表明c-met分子可接近极化肠细胞顶端表面附近存在的配体的机制。通过共聚焦和免疫电子显微镜分析,检测到c-met分子的一个子集,其与最近鉴定的肠上皮细胞刷状缘膜中的src相关的胃肠酪氨酸激酶(gtk)共定位。此外,用化学交联剂处理c-met/gtk转染的细胞显示c-met与gtk在体内形成物理复合物。毫不奇怪,用HGF激活受体分子迅速刺激gtk酶活性。类似地,当未转染的原代肝细胞暴露于配体时,发生gtk活性的刺激。这些发现提示了一种模型,其中HGF与腔可接近的c-met结合刺激gtk活性。这种刷状缘相关的c-met-连锁通路可能与一组确定的上皮细胞反应有关。
Hepatocyte growth factor (HGF) elicits pleiotropic cellular responses by binding to c-met, a PTK transmembrane receptor. The recent identification of HGF in fluids which enter the gut lumen suggests a mechanism by which c-met molecules are accessible to ligand that is present near the apical surfaces of polarized enterocytes. A subset of c-met molecules was detected, by confocal and immunoelectron microscopic analysis, which colocalizes with a recently identified src-related gastrointestinal tyrosine kinase (gtk) in the brush border membranes of enterocytes. Furthermore, treatment of c-met/gtk-transfected cells with a chemical cross-linking agent revealed that c-met forms a physical complex with gtk, in vivo. Not surprisingly, activation of the receptor molecules with HGF rapidly stimulated gtk enzymatic activity. Similarly, the stimulation of gtk activity occurred when nontransfected primary hepatocytes were exposed to ligand. These findings suggest a model in which HGF binding to luminally accessible c-met stimulates gtk activity. This brush border-associated c-met-linked pathway may be associated with a defined set of epithelial cell responses.
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