Early signalling mechanism in colonic epithelial cell response to gastrin.
Early signalling mechanism in colonic epithelial cell response to gastrin.
复制标题
结肠上皮细胞对胃泌素反应的早期信号机制。
DOI：
10.1042/bj3110945
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Little,KM
中科院分区：
文献类型：
--
作者：
Yassin,RR;Little,KM
胃泌素激素对胃肠细胞发挥促进生长的作用。结肠上皮细胞响应胃泌素的分子机制仍知之甚少。在这项研究中，我们证明了胃泌素对正常结肠细胞作用的一个新特征，即磷脂酶 C gamma 1 (PLC gamma 1) 酪氨酸的快速磷酸化。由胃泌素引起的 PLC γ 1 的酪氨酸磷酸化是短暂的、浓度依赖性的，并且通过用胃泌素受体拮抗剂丙谷胺、酪氨酸激酶抑制剂金雀异黄素预处理结肠细胞以及通过从分离缓冲液中去除酪氨酸磷酸酶抑制剂原钒酸盐来消除该酪氨酸磷酸化。 PLC gamma 1 的酪氨酸磷酸化与膜磷脂酰肌醇 4,5-二磷酸 (PIP2) 质量的时间和浓度依赖性下降以及肌醇 1,4,5-三磷酸 (IP3) 上皮浓度的增加相关。同样，丙谷胺和染料木黄酮也阻止了 IP3 的刺激增加。胃泌素诱导细胞内游离 Ca2+ [Ca2+]i 浓度明显但短暂的增加，并增加免疫反应性 α 和 β 蛋白激酶 C 的膜易位。因此，数据表明，胃泌素通过 PLC gamma 1 的快速酪氨酸磷酸化，引发至少一个信号级联，导致 PIP2 特异性 PLC 途径的激活。
The hormone gastrin exerts a growth-promoting effect on gastrointestinal cells. The molecular mechanisms by which colonic epithelial cells respond to gastrin are still poorly understood. In this study, we demonstrate a novel feature of the action of gastrin on normal colonic cells, namely the rapid phosphorylation on tyrosine of phospholipase C gamma 1 (PLC gamma 1). Tyrosine phosphorylation of PLC gamma 1, elicited by gastrin, was transient, concentration-dependent, and was abrogated by pretreating the colonic cells with the gastrin-receptor antagonist proglumide, the tyrosine kinase inhibitor genistein, and by removal of the tyrosine phosphatase inhibitor orthovanadate from the isolation buffer. Tyrosine phosphorylation of PLC gamma 1 correlated with the time- and concentration-dependent decrease in the mass of membrane phosphatidylinositol 4,5-bisphosphate (PIP2) and the increase in the epithelial concentration of inositol 1,4,5-trisphosphate (IP3). Likewise, the stimulated increase in IP3 was also prevented by proglumide and genistein. Gastrin induced a definite but transient increase in the intracellular concentration of free Ca2+ [Ca2+]i, and increased membrane-translocation of immunoreactive alpha- and beta-protein kinase C. The data thus indicate that gastrin elicits at least one signalling cascade, through rapid tyrosine phosphorylation of PLC gamma 1, leading to the activation of a PIP2-specific PLC pathway.