Regulation of protein transport and neuroendocrine secretion by the ARF1-PKD complex at the Trans-Golgi network

高尔基体网络中 ARF1-PKD 复合物对蛋白质运输和神经内分泌分泌的调节

• 批准号: 211407159
• 负责人: Professor Dr. Thomas Seufferlein
• 金额: --
• 依托单位: Abteilung Pharmazeutische Chemie & Bioanalytik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/211407159?language=en
• 关键词: Regulation; protein; transport; neuroendocrine; secretion

The serine/threonine protein kinase D (PKD) family regulates various cellular functions including the fission of transport carriers at the Trans Golgi network (TGN). Thus, PKDs control a central mecha-nism that is crucial for both constitutive and regulated secretion. This mechanism can even constitute a therapeutic target, e.g. in hypersecretory states, such as the Carcinoid syndrome as we have shown previously. However, the precise mechanisms by which PKDs regulate the fission of transport carriers at the TGN are still incompletely understood. Previously we have shown that PKDs interact with ARF GTPases and that this interaction is required for their function at the TGN. In this proposal we will de-termine the precise role of the interaction between ARF1 and PKDs at the TGN and identify further interacting proteins and potential effectors leading to vesicle shedding at the TGN using state of the art techniques including peptide mass fingerprint analysis.

丝氨酸/苏氨酸蛋白激酶D （PKD）家族调节多种细胞功能，包括Trans高尔基网络（TGN）转运载体的裂变。因此，pkd控制着一个对构成和调节分泌都至关重要的中心机制。这种机制甚至可以构成一个治疗靶点，例如在高分泌状态下，如我们之前所展示的类癌综合征。然而，pkd调控转运载体在TGN中的裂变的确切机制仍然不完全清楚。以前我们已经证明pkd与ARF GTPases相互作用，并且这种相互作用是它们在TGN上发挥作用所必需的。在本提案中，我们将确定ARF1和pkd在TGN上相互作用的确切作用，并使用包括肽质量指纹分析在内的最先进技术鉴定导致TGN上囊泡脱落的进一步相互作用蛋白和潜在效应物。

项目成果

Protein Interaction Network of Human Protein Kinase D2 Revealed by Chemical Cross-Linking/Mass Spectrometry.

• DOI: 10.1021/acs.jproteome.6b00513
• 发表时间: 2016-09
• 期刊: Journal of proteome research
• 影响因子: 4.4
• 作者: Björn Häupl;C. Ihling;A. Sinz