通过EGF和胰岛素信号通路激活化醇5-酸酶SHIP2的差异激活

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Updated: Sep 20, 2025

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

Amir Damouni¹, Dániel J Tóth², Szilvia Barsi¹

¹Department of Physiology, Faculty of Medicine, Semmelweis University, Budapest, Hungary.

The Journal of biological chemistry

|May 24, 2025

概括

这项研究揭示了表皮生长因子 (EGF) 和胰岛素是如何独特地调节细胞信号脂质脂酸3,4-双酸盐[PI(3,4) P2]和酸3,4,5-三酸盐 (PIP3) 的. 在EGF信号发送期间,SHIP2被确定为PI(3,4) P2生产的关键.

科学领域:

细胞生物学细胞生物学
分子信号传输的方法
生物化学生化学

背景情况:

酸3,4,5-三酸盐 (PIP3) 对于细胞信号传递至关重要.
酸丁3,4-双酸盐[PI(3,4) P2]的独立作用和动态尚不清楚,特别是在对受体氨酸激酶 (RTK) 刺激的反应中.

研究的目的:

调查PI,P3,P4和PIP3在对EGF和胰岛素的反应中的不同动态.
确定调节PI{3,4) P2生产的关键酶.
阐明这些酶的调节机制.

主要方法:

使用生物发光共振能量转移 (BRET) 传感器来监测等离子体膜中的酸 (PIP) 动态.
采用siRNA介导的敲除方法来识别关键酶.
进行生物信息学分析和西式斑点测试以评估蛋白质酸化.

主要成果:

在EGF和胰岛素刺激下观察到PI{3,4) P2和PIP3水平的差异调节,在EGF下PI{3,4) P2增加更大.
鉴定了含有伊诺西多酸5-酸酶2 (SHIP2) 的SH2域,作为EGF通路中PI(3,4) P2生成的关键酶.
在EGF刺激时检测到SHIP2酸化的增加,这取决于PI3K激活和PLC诱导的信号.

结论:

这些发现澄清了受体特异性酸的动态,并突出了SHIP2在EGF中介信号传输中的作用.
阐明了涉及PI3K和SHIP2激活中的信号的调节机制.
提供了关于这些氏化物差异如何影响下游细胞反应的见解.

关键词:

飞船2号是我们的船.生物发光共振传输能量转移.生物传感器生物传感器皮肤上生长因子受体.胰岛素受体的胰岛素受体酸氨基化物3-酶.酸 3,4-双酸盐是酸 3,4-双酸中的一种.酸的含量是多少酸受体氨酸激酶的受体.

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