Regulation of EGFR signaling in C. Elegans

线虫中 EGFR 信号传导的调节

基本信息

批准号：
7644961
负责人：
Andres Villu Maricq
金额：
$ 26.58万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-07-01 至 2010-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Our long-term goal is to elucidate the mechanisms that regulate growth factor signaling during development. Complex regulatory networks help create the correct signaling intensities underlying specific cell fate decisions, and provide the flexibility to allow cell fate decisions to be coordinated and modulated by environmental and physiological cues. Deregulation of growth factor signaling is linked to many/forms of human cancer. We study regulation of signaling by the epidermal growth factor receptor (EGFR), which is the prototypical evolutionary conserved growth factor receptor, and is the receptor implicated in the widest number of human cancers. Regulation of EGFR signaling can be broadly grouped into 3 layers. These include intramolecular inhibition in key components of the signaling pathway; regulation by trans-acting factors within cells responding to the EGFR; and regulation through cell-cell communication and cross-talk with other signaling pathways. We have developed novel methods for identifying mechanisms that regulate EGFR signaling during vulval development in the nematode C. elegans. Precise patterning of the vulva requires EGFR signaling to be subjected to all 3 layers of regulation. Small deviations from this regulation result in quantifiable changes in vulval patterning. In this proposal, we study 3 new regulatory mechanisms. We will use molecular, genetic, and biochemical approaches to: (1) determine how intramolecular inhibition of SOS, a key component of the EGFR pathway, helps regulate EGFR signaling intensity; (2) determine how the CLR-1 receptor protein tyrosine phosphatase inhibits EGFR signaling; and (3) determine how the new locus, ear-1, regulates EGFR signaling during vulval cell fate specification.

描述（由申请人提供）：我们的长期目标是阐明调节开发过程中生长因子信号的机制。复杂的监管网络有助于创建特定细胞命运决策的基础的正确信号传导强度，并提供灵活性，以允许通过环境和生理提示协调和调节细胞命运决策。生长因子信号传导的放松管制与许多/形式的人类癌症有关。我们研究表皮生长因子受体（EGFR）对信号的调节，这是原型进化保守生长因子受体，并且是与最宽的人类癌症有关的受体。 EGFR信号的调节可以大致分为3层。这些包括在信号通路的关键成分中分子内抑制作用；通过对EGFR响应的细胞内的反式因子调节；并通过细胞电池通信和与其他信号通路进行串扰。我们开发了新的方法，用于识别线虫线虫C.秀隐杆菌外阴发育过程中调节EGFR信号传导的机制。外阴的精确图案要求EGFR信号受到所有3层调节。与此法规的小偏差导致外阴模式的可量化变化。在此提案中，我们研究了3种新的监管机制。我们将使用分子，遗传和生化方法来：（1）确定分子内分子抑制SOS是EGFR途径的关键成分，有助于调节EGFR信号强度；（2）确定CLR-1受体蛋白磷酸酶如何抑制EGFR信号传导；（3）确定新的基因座EAR-1如何调节外阴细胞命运规范期间的EGFR信号传导。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

An activating mutation in sos-1 identifies its Dbl domain as a critical inhibitor of the epidermal growth factor receptor pathway during Caenorhabditis elegans vulval development.

sos-1 的激活突变将其 Dbl 结构域识别为秀丽隐杆线虫外阴发育过程中表皮生长因子受体途径的关键抑制剂。

DOI：
10.1128/mcb.01630-06
发表时间：
2007
期刊：
Molecular and cellular biology
影响因子：
5.3
作者：
Modzelewska,Katarzyna;Elgort,MarcG;Huang,Jingyu;Jongeward,Gregg;Lauritzen,Amara;Yoon,CharlesH;Sternberg,PaulW;Moghal,Nadeem
通讯作者：
Moghal,Nadeem

The SWI/SNF chromatin remodeling complex exerts both negative and positive control over LET-23/EGFR-dependent vulval induction in Caenorhabditis elegans.