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Emerging roles of PHLPP phosphatases in metabolism
Jong-Ho Cha1,2 (Professor), Yelin Jeong1,2,3 (Graduate student), Ah-Reum Oh1,2,3 (Research worker), Sang Bae Lee4,5 (Professor), Soon-Sun Hong1,2,3 (Professor), KyeongJin Kim 1,2,3,* (Professor)
1Department of Biomedical Sciences, College of Medicine, Inha University, Incheon 22212, South Korea,
2Program in Biomedical Science & Engineering, Inha University, Incheon 22212, South Korea, South Korea,
3Research Center for Controlling Intercellular Communication (RCIC), College of Medicine, Inha University, Incheon 22212, South Korea,
4Division of Life Sciences, Jeonbuk National University, Jeonju 54896, South Korea,
5Sarcopenia Total Solution Center, onkwang University School of Medicine, Iksan, Jeonbuk 54538, South Korea
Abstract
Over the last decades, research has focused on the role of pleckstrin homology (PH) domain leucine-rich repeat protein phosphatases (PHLPPs) in regulating cellular signaling via PI3K/Akt inhibition. The PKB/Akt signaling imbalances are associated with a variety of illnesses, including various types of cancer, inflammatory response, insulin resistance, and diabetes, demonstrating the relevance of PHLPPs in the prevention of diseases. Furthermore, identification of novel substrates of PHLPPs unveils their role as a critical mediator in various cellular processes. Recently, researchers have explored the increasing complexity of signaling networks involving PHLPPs whereby relevant information of PHLPPs in metabolic diseases were obtained. In this review, we discuss the current knowledge of PHLPPs on the well-known substrates and metabolic regulation, especially in liver, pancreatic beta cell, adipose tissue, and skeletal muscle in relation with the stated diseases. Understanding the context-dependent functions of PHLPPs can lead to a promising treatment strategy for several kinds of metabolic diseases.
Abstract, Accepted Manuscript(in press) [Submitted on July 16, 2021, Accepted on July 27, 2021]
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