p38和与p38相互作用的蛋白质对于在小鼠胃化过程中对E-cadherin的下调至关重要
Irene E Zohn1, Yingqiu Li, Edward Y Skolnik
1Howard Hughes Medical Institute, Department of Pediatrics, Section of Developmental Biology, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, USA.
p38 MAP 激酶和p38 相互作用蛋白 (p38IP) 通过降低 E-cadherin 的调节,对于脊椎动物胃流动期间的中皮层迁移至关重要. 在p38IP中的突变破坏了这个过程,导致发育缺陷.
科学领域:
- 发育生物学 发展生物学
- 细胞信号传递 细胞信号传递
- 分子遗传学 分子遗传学
背景情况:
- 脊椎动物的胃化涉及表皮细胞到介质细胞的过渡 (EMT),用于介质体的迁移.
- 在消化过程中,对EMT而言,E-cadherin的降低调节至关重要.
- 在这个过程中,p38 MAP 激酶及其相互作用蛋白的作用需要进一步阐明.
研究的目的:
- 调查p38 MAP激酶和p38相互作用蛋白 (p38IP) 在胃流动期间E-cadherin下调中的作用.
- 确定影响p38IP功能的遗传因素及其对胚胎发育的影响.
主要方法:
- ENU-突变发生屏幕用于识别影响p38IP的突变.
- 对发育缺陷的突变胚胎 (p38IP,p38IP,RRK) 的分析.
- 生物化学测试以确定p38IP与p38的相互作用及其在p38激活中的作用.
- 研究E-cadherin蛋白水平和p38和p38IP的调节.
主要成果:
- 垂落眼 (干燥) 突变影响p38IP拼接,导致发育缺陷.
- 较强的p38IP突变会导致胃化缺陷,原因是中皮迁移受损和E-cadherin下调.
- p38IP直接与p38结合,并且是活体中p38激活所必需的.
- 在胃流动过程中,p38和p38IP都对E-cadherin下调有必要.
- p38调节NCK相互作用激酶 (NIK) 下游的E-cadherin蛋白表达,并且独立于Fgf信号和Snail.
结论:
- p38 MAP 激酶和p38IP是脊椎动物胃流动期间E-cadherin下调的关键调节者.
- 在体内,p38IP充当了p38信号的支架或激活器.
- 干扰p38/p38IP通路会导致胃化缺陷,因为会影响中皮层的迁移.
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