Project# 4: INTERACTIONS OF ANCHORING PROTEINS WITH THEIR TARGETS

蛋白激酶和磷酸酶的正确细胞内靶向赋予了这些酶的特异性，在 将它们放置在靠近它们喜欢的底物的地方。这些酶的靶向是通过联合 在细胞的不同位置发现的特定蛋白质。我们研究进展的中心主题？ 了解调节活动和时空组织的结构基础以及 和脂质第二信使信号级联。特别是，特定对象之间交互作用的变化 合作伙伴可以改变各自蛋白激酶(PKs)的生命周期和/或亚细胞定位。在这 应用，我们建议利用我们在结构和动态特性方面所取得的进展 PKA调节亚基的I型和II型二聚化和对接(DID)结构域与 锚定伙伴、Pro异构化在调节PKC生命周期中的调节作用及其作用 范围串扰在调节I型PKA活性的特异性靶点。 我们的具体目标是： I.阐明I型和II型PKA异构体特异性靶向的结构基础 了解特定的蛋白质结合伙伴如何调节分子开关事件！ PKC的生命周期 和 研究锚定的PKA在调节其结构和活性中的作用 线粒体上的底物

The correct intracellular targeting of protein kinases and phosphatases confers specificity to the enzymes, in placing them in close proximity to their preferred substrates. Targeting of these enzymes occurs via associati specific proteins which are found in different locations in the cell. The central theme of our research progr^ understand the structural basis for the regulation of the activity and spatiotemporal organization and of th and lipid second messenger signaling cascades. In particular, changes in interactions between specific partners can alter the lifecycle and/or subcellular localization of the respective protein kinases (PKs). In this application, we propose to capitalize on the progress we have made in the structural and dynamic characteriz the type I and type II dimerization and docking (DID) domains of the regulatory subunits of PKA with anchoring partners, the regulatory role of proline isomerization in regulating the PKC lifecycle and the role range crosstalk in regulating the activity of type I PKA specific targets. Our Specific Aims are directed towards: I. Elucidating the Structural Basis for the Isoform-Specific Targeting of Type I andType II PKA II. Understanding How Specific Protein Binding Partners Regulate Molecular Switching Event! Lifecycle of PKC And III. Investigating the Role of Anchored PKA in Regulating the Structure and Activity of its Substrates at the Mitochondria