Wang Qiming J
Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Trends Pharmacol Sci. 2006 Jun;27(6):317-23. doi: 10.1016/j.tips.2006.04.003. Epub 2006 May 6.
Diacylglycerol (DAG) and its primary target protein kinase C (PKC) regulate many important cellular responses, yet the molecular mechanisms that control the specificity of DAG and PKC signaling are not fully understood. As such, targeting the PKC pathway for therapeutic purposes has been challenging. Protein kinase D (PKD), a novel DAG receptor, has been the subject of intense investigation in recent years. DAG regulates the intracellular localization of PKD and also activates PKD through PKC by phosphorylation. The PKC-PKD signaling cascade is crucial to PKD function in cells. Important discoveries have been made regarding the roles of PKD in cell growth, gene expression, survival, motility, protein trafficking and lymphocyte biology. This kinase is implicated in pathological processes such as cardiac hypertrophy, tumor cell proliferation and metastasis. Thus, PKD represents a novel therapeutic target for the DAG-PKC signaling network.
二酰基甘油（DAG）及其主要靶标蛋白激酶C（PKC）调节许多重要的细胞反应，但控制DAG和PKC信号特异性的分子机制尚未完全明确。因此，将PKC途径作为治疗靶点颇具挑战性。蛋白激酶D（PKD）作为一种新型DAG受体，近年来一直是深入研究的对象。DAG调节PKD的细胞内定位，并通过PKC磷酸化激活PKD。PKC-PKD信号级联对于PKD在细胞中的功能至关重要。关于PKD在细胞生长、基因表达、存活、迁移、蛋白质运输和淋巴细胞生物学中的作用已取得重要发现。这种激酶与诸如心脏肥大、肿瘤细胞增殖和转移等病理过程有关。因此，PKD是DAG-PKC信号网络的一个新型治疗靶点。
