Cancer: MAPK phosphorylation and nuclear translocation

癌症：MAPK 磷酸化和核易位

• 批准号: 6993753
• 负责人: Daniel R Marenda
• 金额: $ 4.09万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6993753
• 关键词: Drosophilidae; arthropod genetics; biological signal transduction; cell differentiation; cell growth regulation; cell proliferation; gene expression; genetic screening; mitogen activated protein kinase; molecular oncology; phenotype; phosphorylation; postdoctoral investigator; protein localization; protein transport

DESCRIPTION (provided by applicant): Mitogen-activated protein kinases (MAPKs) are a highly conserved family of protein serine/ threonine kinases involved in signal transduction pathways in yeast, flies, and mammals, and are activated in response to a variety of signals. In mammals, MARK proteins p42/p44 (also called ERK 1/2) phosphorylate and activate a number of targets in both the cytoplasm and the nucleus, and in cell culture systems, a strong correlation exists between the subcellular localization of MAPK and the subsequent cellular responses elicited. However, preliminary data from our lab suggests that MAPK can function to promote cell proliferation after translocation to the nucleus even when it does not become phosphorylated. I therefore plan to test this suggestion directly, with the following two specific aims: 1) Is MAPK phosphorylation required for MAPK nuclear translocation and cell cycle progression?, and 2) What are the factors mediating MAPK hold in the cyoplasm vs. translocation to the nucleus in cell cycle regulation? As alterations in the Ras/MAPK pathway are associated with approximately 25% of human tumors, a deeper understanding of how MAPK nuclear translocation affects this process could enhance our understanding of human cancers.

描述（由申请人提供）：有丝分裂原激活的蛋白激酶（MAPKS）是高度保守的蛋白质丝氨酸/苏氨酸激酶，参与酵母，苍蝇和哺乳动物中信号转导途径的蛋白质/苏氨酸激酶，并因各种信号而被激活。在哺乳动物中，标记蛋白p42/p44（也称为ERK 1/2）磷酸化并激活细胞质和细胞核中的许多靶标，以及在细胞培养系统中，MAPK的亚细胞定位与随后的细胞响应之间存在很强的相关性。但是，我们实验室的初步数据表明，即使未变成磷酸化，MAPK也可以在迁移到核后促进细胞增殖。因此，我计划直接测试这一建议，以下两个具体目的：1）MAPK核易位和细胞周期进程所需的MAPK磷酸化是否需要？和2）介导MAPK在细胞周期调节中介导MAPK的因素是什么？由于RAS/MAPK途径的改变与大约25％的人类肿瘤有关，因此对MAPK核转运如何影响这一过程的更深入了解可以增强我们对人类癌症的理解。

项目成果

Delta and Egfr expression are regulated by Importin-7/Moleskin in Drosophila wing development.

• DOI: 10.1016/j.ydbio.2007.06.011
• 发表时间: 2007-08
• 期刊: Developmental biology
• 影响因子: 2.7
• 作者: A. Vrailas-Mortimer;N. Majumdar;Ginnene Middleton;Evan M Cooke;Daniel R. Marenda