Department of Pharmacology, University of California, San Diego, La Jolla, CA 92039, USA.
Department of Pharmacology, University of California, San Diego, La Jolla, CA 92039, USA; Cardiovascular Molecular Signaling, Huntington Medical Research Institutes, Pasadena, CA 91105, USA.
Cell Signal. 2021 Oct;86:110097. doi: 10.1016/j.cellsig.2021.110097. Epub 2021 Jul 25.
PH domain leucine-rich repeat protein phosphatase (PHLPP) is a family of enzymes made up of two isoforms (PHLPP1 and PHLPP2), whose actions modulate intracellular activity via the dephosphorylation of specific serine/threonine (Ser/Thr) residues on proteins such as Akt. Recent data generated in our lab, supported by findings from others, implicates the divergent roles of PHLPP1 and PHLPP2 in maintaining cellular homeostasis since dysregulation of these enzymes has been linked to various pathological states including cardiovascular disease, diabetes, ischemia/reperfusion injury, musculoskeletal disease, and cancer. Therefore, development of therapies to modulate specific isoforms of PHLPP could prove to be therapeutically beneficial in several diseases especially those targeting the cardiovascular system. This review is intended to provide a comprehensive summary of current literature detailing the role of the PHLPP isoforms in the development and progression of heart disease.
PH 结构域亮氨酸丰富重复蛋白磷酸酶（PHLPP）是由两种同工酶（PHLPP1 和 PHLPP2）组成的酶家族，其作用通过去磷酸化 Akt 等蛋白质上的特定丝氨酸/苏氨酸（Ser/Thr）残基来调节细胞内活性。我们实验室最近生成的数据，以及其他研究的发现，表明 PHLPP1 和 PHLPP2 在维持细胞内稳态方面具有不同的作用，因为这些酶的失调与各种病理状态有关，包括心血管疾病、糖尿病、缺血/再灌注损伤、肌肉骨骼疾病和癌症。因此，开发调节 PHLPP 特定同工型的疗法可能在几种疾病中具有治疗益处，特别是针对心血管系统的疾病。本综述旨在提供对目前文献的全面总结，详细阐述 PHLPP 同工型在心脏病发展和进展中的作用。
