Multifaceted Functions of Protein Kinase D in Pathological Processes and Human Diseases.
Multifaceted Functions of Protein Kinase D in Pathological Processes and Human Diseases.
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DOI：
10.3390/biom11030483
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发表时间：
2021-03-23
期刊：
影响因子：
5.5
通讯作者：
Wang QJ
中科院分区：
文献类型：
--
作者：
Zhang X;Connelly J;Chao Y;Wang QJ
蛋白激酶D（PKD）是一个在第二信使二酰甘油信号网络中发挥作用的丝氨酸/苏氨酸蛋白激酶家族。三个家族成员PKD 1、PKD 2和PKD 3被多种细胞外刺激和巨噬细胞信号激活，影响基本细胞功能的许多方面，包括分泌、迁移、增殖、存活、血管生成和免疫应答。PKD的表达和活性失调已在许多人类疾病中被检测到。在细胞水平和动物模型中进一步的功能丧失或获得研究为PKD在许多病理条件中的关键作用提供了强有力的支持，包括癌症、代谢紊乱、心脏病、中枢神经系统疾病、炎性疾病和免疫失调。酶调节和功能的复杂性是显而易见的，因为PKD亚型在不同的生物系统和疾病模型中可能会有不同的作用，了解这些差异的分子机制及其在体内的生物学意义对于开发更安全，更有效的PKD靶向治疗至关重要。在这篇综述中，为了提供对PKD功能的全面了解，我们概述了PKD家族在几种主要人类疾病中的作用，更侧重于癌症相关的生物学过程。
Protein kinase D (PKD) is a family of serine/threonine protein kinases operating in the signaling network of the second messenger diacylglycerol. The three family members, PKD1, PKD2, and PKD3, are activated by a variety of extracellular stimuli and transduce cell signals affecting many aspects of basic cell functions including secretion, migration, proliferation, survival, angiogenesis, and immune response. Dysregulation of PKD in expression and activity has been detected in many human diseases. Further loss- or gain-of-function studies at cellular levels and in animal models provide strong support for crucial roles of PKD in many pathological conditions, including cancer, metabolic disorders, cardiac diseases, central nervous system disorders, inflammatory diseases, and immune dysregulation. Complexity in enzymatic regulation and function is evident as PKD isoforms may act differently in different biological systems and disease models, and understanding the molecular mechanisms underlying these differences and their biological significance in vivo is essential for the development of safer and more effective PKD-targeted therapies. In this review, to provide a global understanding of PKD function, we present an overview of the PKD family in several major human diseases with more focus on cancer-associated biological processes.
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