ArticleCell death & disease2021
Phosphatase PHLPP2 regulates the cellular response to metabolic stress through AMPK.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Phase separation of MARCH1 promotes rectal adenocarcinoma progression through PHLPP2 ubiquitination.Translational cancer research · 2026Article
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- Novel Micro-Ribonucleic Acid Biomarkers for Early Detection of Type 2 Diabetes Mellitus and Associated Complications-A Literature Review.International journal of molecular sciences · 2025Review
- AMPK in Intestinal Health and Disease: A Multifaceted Therapeutic Target for Metabolic and Inflammatory Disorders.Drug design, development and therapy · 2025Review
- Protein phosphatase 4 maintains the survival of primordial follicles by regulating autophagy in oocytes.Cell death & disease · 2024Article
- Review
- RNA-Seq-based discovery of genetic variants and allele-specific expression of two layer lines and broiler chicken.Evolutionary applications · 2023Article
- New insights into activation and function of the AMPK.Nature reviews. Molecular cell biology · 2023Review
- Circular RNA ANAPC7 Inhibits Tumor Growth and Muscle Wasting via PHLPP2-AKT-TGF-β Signaling Axis in Pancreatic Cancer.Gastroenterology · 2022Article
- PHLPP1 promotes neutral lipid accumulation through AMPK/ChREBP-dependent lipid uptake and fatty acid synthesis pathways.iScience · 2022Article
- Exosomal EPHA2 derived from highly metastatic breast cancer cells promotes angiogenesis by activating the AMPK signaling pathway through Ephrin A1-EPHA2 forward signaling.Theranostics · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
PHLPP2 is a member of the PHLPP family of phosphatases, known to suppress cell growth by inhibiting proliferation or promoting apoptosis. Oncogenic kinases Akt, S6K, and PKC, and pro-apoptotic kinase Mst1, have been recognized as functional targets of the PHLPP family. However, we observed that, in T-leukemia cells subjected to metabolic stress from glucose limitation, PHLPP2 specifically targets the energy-sensing AMP-activated protein kinase, pAMPK, rather than Akt or S6K. PHLPP2 dephosphorylates pAMPK in several other human cancer cells as well. PHLPP2 and pAMPK interact with each other, and the pleckstrin homology (PH) domain on PHLPP2 is required for their interaction, for dephosphorylating and inactivating AMPK, and for the apoptotic response of the leukemia cells to glucose limitation. Silencing PHLPP2 protein expression prolongs the survival of leukemia cells subjected to severe glucose limitation by promoting a switch to AMPK-mediated fatty acid oxidation for energy generation. Thus, this study reveals a novel role for PHLPP2 in suppressing a survival response mediated through AMPK signaling. Given the multiple ways in which PHLPP phosphatases act to oppose survival signaling in cancers and the pivotal role played by AMPK in redox homeostasis via glucose and fatty acid metabolism, the revelation that AMPK is a target of PHLPP2 could lead to better therapeutics directed both at cancer and at metabolic diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.