Crosstalk between cAMP and ERK signalling pathways in tubulogenesis

肾小管发生中 cAMP 和 ERK 信号通路之间的串扰

• 批准号: 73357210
• 负责人: Dr. Pavel Nedvetsky
• 金额: --
• 依托单位: Department of Anatomy
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/73357210?language=en
• 关键词: Crosstalk; between; cAMP; ERK; signalling

Tubulogenesis is fundamental to the development of epithelial organs. Madin-Darby canine kidney (MDCK) cells growing in 3 dimensional (3D) thick collagen gels represent a useful simplified model, where tubulogenesis can be studied. In this system, tubulogenesis could be induced by treatment of the cells with Hepatocyte Growth Factor (HGF). Downstream signaling pathways involved in the regulation of tubulogenesis are under intensive investigation. It has been demonstrated that prolonged ERK activation is a key event in this process. Therefore, identification of signaling pathways resulting in modulation of ERK activity during tubulogenesis is of fundamental significance. Surprisingly little is known about the role of the important second messenger cyclic AMP (cAMP) during tubulogenesis. In the present project the role of cAMP in regulation of tubulogenesis and its crosstalk with ERK signaling will be studied. Three major questions will be addressed: (i) what role does cAMP play in tubulogenesis; (ii) is there a crosstalk between cAMP-dependent signaling and ERK pathway; (iii) which role does the compartmentalization of cAMP signaling play.

小管发生是上皮器官发育的基础。Madin-Darby犬肾（MDCK）细胞生长在3维（3D）厚胶原凝胶代表了一个有用的简化模型，其中可以研究肾小管发生。在该系统中，可以通过用肝细胞生长因子（HGF）处理细胞来诱导微管发生。下游信号通路参与调控的tubulogenesis正在深入调查。已经证明，延长ERK激活是该过程中的关键事件。因此，在微管形成过程中，识别导致ERK活性调节的信号通路具有重要意义。令人惊讶的是，很少有人知道的作用，重要的第二信使环磷酸腺苷（cAMP）在肾小管。在本项目中，cAMP的作用，在调控的小管和它的串扰与ERK信号将被研究。将解决三个主要问题：（i）什么样的作用cAMP在肾小管生成;（ii）cAMP依赖的信号转导和ERK通路之间是否存在串扰;（iii）cAMP信号转导的区室化发挥什么作用。