An Innovative Approach for Profiling Protein Kinase Substrates

分析蛋白激酶底物的创新方法

• 批准号: 7916888
• 负责人: CHARLES J. BIEBERICH
• 金额: $ 2.61万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE COUNTY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-10 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7916888
• 关键词: Biological; Biological Assay; Biological Process; Cells; Classification; Complex; Data; Disease; Etiology; Gel; Goals; In Vitro; LNCaP; Laboratories; Libraries; Malignant Neoplasms; Methods; Phosphorylation; Phosphotransferases; Physiological; Play; Protein Kinase; Protein-Serine-Threonine Kinases; Proteins; Role; Signal Pathway; Signal Transduction; Stimulus; System; Techniques; Technology; Therapeutic Intervention; Validation; casein kinase II; innovation; novel; research study; response

DESCRIPTION (provided by applicant): Signal transduction is a central component of nearly all biological processes. Protein kinases play critical roles in signaling pathways by phosphorylating proteins involved in signal amplification and in executing the cellular response to extrinsic or intrinsic stimuli. Aberrant kinase signaling plays a role in the etiology of nearly all cancers and in hundreds of other diseases. Systematic approaches to the elucidation of the signaling pathways driven by kinases have the potential to illuminate new points of therapeutic intervention. The identification of physiologic kinase substrates is an important component of this endeavor. Currently, there is a need for technologies that can be widely deployed to approach this problem. We are developing a simple, straightforward technique for kinase substrate profiling that we term the reverse in-gel kinase assay. This assay enables the discovery of kinase substrates in whole or pre-fractionated complex biological extracts. If properly developed and validated, this assay has the potential, through the concerted effort of multiple laboratories, to enable rapid identification of potential physiologic substrates of many kinases.

描述（由申请人提供）： 信号转导是几乎所有生物过程的核心组成部分。蛋白激酶通过磷酸化参与信号放大和执行细胞对外在或内在刺激的反应的蛋白质，在信号传导通路中发挥关键作用。异常的激酶信号传导在几乎所有癌症和数百种其他疾病的病因学中发挥着重要作用。阐明激酶驱动的信号通路的系统方法有可能阐明治疗干预的新点。生理激酶底物的鉴定是这项工作的重要组成部分。目前，需要可以广泛部署的技术来解决这个问题。我们正在开发一种简单、直接的激酶底物分析技术，我们将其称为反向凝胶内激酶测定。该测定能够发现完整或预分馏的复杂生物提取物中的激酶底物。如果得到适当的开发和验证，通过多个实验室的共同努力，该测定有可能能够快速识别许多激酶的潜在生理底物。

项目成果

Identification and validation of inhibitor-responsive kinase substrates using a new paradigm to measure kinase-specific protein phosphorylation index.

• DOI: 10.1021/pr3000514
• 发表时间: 2012-07-06
• 期刊: Journal of proteome research
• 影响因子: 4.4
• 作者: Li X;Rao V;Jin J;Guan B;Anderes KL;Bieberich CJ
• 通讯作者: Bieberich CJ