...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) integrates developmental signals for eyelid closure
【24h】

Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) integrates developmental signals for eyelid closure

机译：丝裂原激活的蛋白激酶激酶激酶1（MAP3K1）整合了眼睑闭合的发育信号

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Developmental eyelid closure is an evolutionary conserved morphogenetic event requiring proliferation, differentiation, cy-toskeleton reorganization, and migration of epithelial cells at the tip of the developing eyelid. Many signaling events take place during eyelid closure, but how the signals converge to regulate the morphogenetic process remains an open and intriguing question. Here we show that mitogen-activated protein kinase kinase kinase 1 (MAP3K1) highly expressed in the developing eyelid epithelium, forms with c-Jun, a regulatory axis that orchestrates morphogenesis by integrating two different networks of eyelid closure signals. A TGF-α/EGFR-RhoA module initiates one of these networks by inducing c-Jun expression which, in a phos-phorylation-independent manner, binds to the Map3k1 promoter and causes an increase in MAP3K1 expression. RhoA knockout in the ocular surface epithelium disturbs this network by decreasing MAP3K1 expression, and causes delayed eyelid closure in Map3k1 hemizygotes. The second network is initiated by the enzymatic activity of MAP3K1, which phosphorylates and activates a JNK-c-Jun module, leading to AP-1 transactivation and induction of its downstream genes, such as Pai-1. MAP3K1 inactivation reduces AP-1 activity and PAI-1 expression both in cells and developing eyelids. MAP3K1 is therefore the nexus of an intracrine regulatory loop, connecting the TGF-α/EGFR/RhoA-c-Jun and JNK-c-Jun-AP-1 pathways in developmental eyelid closure.
机译：发育性眼睑闭合是一种进化保守的形态发生事件，需要增殖，分化，cy-骨架重组以及上睑细胞在发育中的眼睑尖端迁移。在眼睑闭合期间发生了许多信号传递事件，但是信号如何收敛以调节形态发生过程仍然是一个开放而有趣的问题。在这里，我们显示了在发展中的眼睑上皮中高度表达的促分裂原活化蛋白激酶激酶激酶1（MAP3K1）与c-Jun形成，c-Jun是通过整合两个不同的眼睑闭合信号网络来协调形态发生的调控轴。 TGF-α/ EGFR-RhoA模块通过诱导c-Jun表达来启动这些网络之一，该c-Jun表达以磷酸磷酸化独立的方式与Map3k1启动子结合并导致MAP3K1表达增加。眼表面上皮细胞中的RhoA基因敲除通过降低MAP3K1表达而干扰了该网络，并导致Map3k1半合子的眼睑延迟闭合。第二个网络是由MAP3K1的酶促活性引发的，MAP3K1磷酸化并激活JNK-c-Jun模块，从而导致AP-1反式激活并诱导其下游基因（如Pai-1）。 MAP3K1失活会降低细胞和发育中的眼睑的AP-1活性和PAI-1表达。因此，MAP3K1是内分泌调节环的连接，在发育性眼睑闭合中连接了TGF-α/ EGFR / RhoA-c-Jun和JNK-c-Jun-AP-1途径。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号