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）家族调节各种细胞功能，包括在反式高尔基网络（TGN）上裂变运输载体。因此，PKD控制着中央机制 - 基因，这对于本构和调节的分泌至关重要。这种机制甚至可以构成一个治疗靶点，例如如我们先前所显示的，在高度分泌状态中，例如类癌综合征。但是，仍然尚不完全了解PKD调节TGN运输载体裂变的确切机制。以前，我们已经证明了PKD与ARF GTPases相互作用，并且这种相互作用是其在TGN的功能所必需的。在此提案中，我们将使用包括肽质量指纹分析的最先进的技术来删除TGN ARF1与PKD之间相互作用的确切作用，并确定进一步的相互作用蛋白质和潜在的效应子。

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