Protein Tyrosine Phosphatase 1B Regulates Pyruvate Kinase M2 Tyrosine Phosphorylation

Bettaieb, Ahmed; Bakke, Jesse; Nagata, Naoto; Matsuo, Kazuya; Xi, Yannan; Liu, Siming; AbouBechara, Daniel; Melhem, Ramzi; Stanhope, Kimber L.; Cummings, Bethany P.; Graham, James L.; Bremer, Andrew A.; Zhang, Sheng; Lyssiotis, Costas A.; Zhang, Zhong Yin; Cantley, Lewis C.; Havel, Peter J.; Haj, Fawaz G.

doi:10.1074/jbc.m112.441469

Cited by 50 publications

(48 citation statements)

References 64 publications

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“…In addition, fibroblast growth factor receptor 1 phosphorylates PKM2 on Tyr-105, which inhibits the formation of active, tetrameric PKM2 by disrupting binding of PKM2 cofactor fructose-1,6-biophosphate (17). Protein-tyrosine phosphatase 1B reverses this phosphorylation (18). A-Raf can bind to and phosphorylate PKM2 on serine residues, inducing a transition of dimeric to tetrameric active form of PKM2 (19).…”

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confidence: 99%

“…Compared with normal tissues, most tumors exhibit a significant increase of glucose utilization, namely the Warburg effect (1). Such a characteristic of increased glucose uptake, which accompanies the aerobic glycolysis, has been exploited for diagnosis of cancer using 18 F-deoxyglucose position emission tomography (2). Due to the changes of glycolytic enzymes, tumor cells shift glucose metabolism from oxidative phosphorylation to glycolysis even in the presence of oxygen.…”

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confidence: 99%

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Proviral Insertion in Murine Lymphomas 2 (PIM2) Oncogene Phosphorylates Pyruvate Kinase M2 (PKM2) and Promotes Glycolysis in Cancer Cells

Zhao

Huang

et al. 2013

Journal of Biological Chemistry

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Background:The protein-serine/threonine kinase PIM2 regulates glycolysis, but the mechanism is not fully elucidated. Results: PIM2 interacts with PKM2 and phosphorylates PKM2 on the Thr-454 residue. Conclusion: This phosphorylation of PKM2 increases glycolysis and proliferation in cancer cells. Significance: PIM2-dependent phosphorylation of PKM2 is critical for regulating the Warburg effect in cancer, highlighting PIM2 as a potential therapeutic target.

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confidence: 99%

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confidence: 99%

Proviral Insertion in Murine Lymphomas 2 (PIM2) Oncogene Phosphorylates Pyruvate Kinase M2 (PKM2) and Promotes Glycolysis in Cancer Cells

Zhao

Huang

et al. 2013

Journal of Biological Chemistry

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“…Consistent with finding in vitro, quantitative RT-PCR analysis indicated that the expression of CPT1 was significantly increased when HDIO zebrafish was fed 10 µg/mL of FCSN ( Figure 4B). Moreover, we found that 10 µg/mL of FCSN supplemented HDIO zebrafish significantly induced the increased expression of pyruvate kinase M2 (PK-M2), which decrease in adipose tissue in obese animal model [31], compared to HDIO zebrafish. Here, we provided a part of evidence that FCSN may lead to suppress body fat accumulation through stimulating both energy metabolism and β-oxidation in HDIO zebrafish.…”

Section: Effects Of Fcsn On Energy Metabolism and β-Oxidation In Highmentioning

confidence: 93%

Optimized <i>Cirsium setidens</i> Nakai Fermented by <i>Lentinula edodes</i> Attenuates Lipid Accumulation by Regulating Fatty Acid Oxidation-mediated Lipolysis in 3T3-L1 Cells and High Calorie Diet-induced Obese Zebrafish

Kim¹,

Lee²,

Lee³

et al. 2017

JFNR

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Cirsium setidens Nakai is an edible herb. Previously we found that fermented Cirsium setidens Nakai (FCSN) has a large amount of major bioactive compound compared to Cirsium setidens Nakai. In this study, we aimed to examine the anti-obesity effect of FCSN using 3T3-L1 cells in vitro and high calorie diet-induced obese (HDIO) zebrafish model in vivo. Our results demonstrated that FCSN significantly inhibited intracellular lipid accumulation in 3T3-L1 cells. FCSN was shown to reduce the expressions of crucial adipocyte differentiation markers, including PPARγ and aP2. FCSN also decreased the production of ROS due to the up-regulated expressions of SOD1, SOD2, GPx, and catalase. Furthermore, we observed that FCSN also altered the levels of energy metabolism and β-oxidation-associated genes such as AMPK, ACC, and CPT-1. In addition, ATGL, a key lipolysis enzyme, was stimulated while the differentiation of 3T3-L1 was suppressed by FCSN. Strikingly, we found that FCSN dramatically increased both the energy metabolism and β-oxidation associated genes and subsequently prevented the increase of body fat accumulation in high calorie diet-induced obese zebrafish. Taken together, this is the first study that demonstrates that FCSN has the beneficial activity to suppress adipogenesis in 3T3-L1 cells and ameliorate an obese-associated health condition in vivo.

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“…PTP1B-deficient brown adipose tissue [122] and brown adipocytes [81] exhibit increased AMPK activity. In addition, recent studies identify pyruvate kinase M2 (PKM2) as a PTP1B substrate [64]. Pyruvate kinase (PK) is a rate-limiting glycolytic enzyme that catalyzes the generation of pyruvate and ATP from phosphoenolpyruvate (PEP) and ADP [123] (Figure 1).…”

Section: Ptp1b Substrates and Metabolic Regulationmentioning

confidence: 99%

Protein-tyrosine phosphatase 1B substrates and metabolic regulation

Bakke

Haj

2015

Seminars in Cell & Developmental Biology

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Metabolic homeostasis requires integration of complex signaling networks which, when deregulated, contribute to metabolic syndrome and related disorders. Protein-tyrosine phosphatase 1B (PTP1B) has emerged as a key regulator of signaling networks that are implicated in metabolic diseases such as obesity and type 2 diabetes. In this review, we examine mechanisms that regulate PTP1B-substrate interaction, enzymatic activity and experimental approaches to identify PTP1B substrates. We then highlight findings that implicate PTP1B in metabolic regulation. In particular, insulin and leptin signaling are discussed as well as recently identified PTP1B substrates that are involved in endoplasmic reticulum stress response, cell-cell communication, energy balance and vesicle trafficking. In summary, PTP1B exhibits exquisite substrate specificity and is an outstanding pharmaceutical target for obesity and type 2 diabetes.

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Protein Tyrosine Phosphatase 1B Regulates Pyruvate Kinase M2 Tyrosine Phosphorylation

Cited by 50 publications

References 64 publications

Proviral Insertion in Murine Lymphomas 2 (PIM2) Oncogene Phosphorylates Pyruvate Kinase M2 (PKM2) and Promotes Glycolysis in Cancer Cells

Proviral Insertion in Murine Lymphomas 2 (PIM2) Oncogene Phosphorylates Pyruvate Kinase M2 (PKM2) and Promotes Glycolysis in Cancer Cells

Optimized <i>Cirsium setidens</i> Nakai Fermented by <i>Lentinula edodes</i> Attenuates Lipid Accumulation by Regulating Fatty Acid Oxidation-mediated Lipolysis in 3T3-L1 Cells and High Calorie Diet-induced Obese Zebrafish

Protein-tyrosine phosphatase 1B substrates and metabolic regulation

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