Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261, USA.
Department of Anesthesiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Biochim Biophys Acta Rev Cancer. 2017 Aug;1868(1):283-294. doi: 10.1016/j.bbcan.2017.05.008. Epub 2017 May 31.
Protein kinase D is a family of evolutionarily conserved serine/threonine kinases that belongs to the Ca/Calmodulin-dependent kinase superfamily. Signal transduction pathways mediated by PKD can be triggered by a variety of stimuli including G protein-coupled receptor agonists, growth factors, hormones, and cellular stresses. The regulatory mechanisms and physiological roles of PKD have been well documented including cell proliferation, survival, migration, angiogenesis, regulation of gene expression, and protein/membrane trafficking. However, its precise roles in disease progression, especially in cancer, remain elusive. A plethora of studies documented the cell- and tissue-specific expressions and functions of PKD in various cancer-associated biological processes, while the causes of the differential effects of PKD have not been thoroughly investigated. In this review, we have discussed the structural-functional properties, activation mechanisms, signaling pathways and physiological functions of PKD in the context of human cancer. Additionally, we have provided a comprehensive review of the reported tumor promoting or tumor suppressive functions of PKD in several major cancer types and discussed the discrepancies that have been raised on PKD as a major regulator of malignant transformation.
蛋白激酶 D 是一类进化上保守的丝氨酸/苏氨酸激酶，属于钙/钙调蛋白依赖性激酶超家族。PKD 介导的信号转导途径可被多种刺激触发，包括 G 蛋白偶联受体激动剂、生长因子、激素和细胞应激。PKD 的调节机制和生理作用已有详细记录，包括细胞增殖、存活、迁移、血管生成、基因表达调控和蛋白质/膜运输。然而，其在疾病进展中的精确作用，尤其是在癌症中的作用仍不明确。大量研究记录了 PKD 在各种与癌症相关的生物学过程中的细胞和组织特异性表达和功能，而 PKD 产生差异效应的原因尚未得到彻底研究。在这篇综述中，我们讨论了 PKD 在人类癌症中的结构-功能特性、激活机制、信号通路和生理功能。此外，我们还全面回顾了 PKD 在几种主要癌症类型中被报道的促进肿瘤或抑制肿瘤的功能，并讨论了 PKD 作为恶性转化主要调节剂的争议。
