Glycolytic ATP fuels phosphoinositide 3-kinase signaling to support effector T helper 17 cell responses

Xu, Ke; Yin, Na; Peng, Min; Stamatiades, Efstathios G.; Chhangawala, Sagar; Shyu, Amy; Li, Peng; Zhang, Xian; Mytrang, H.; Capistrano, Kristelle J.; Chou, Chun; Leslie, Christina; Li, Ming O.

doi:10.1016/j.immuni.2021.04.008

Cited by 69 publications

(56 citation statements)

References 66 publications

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“… Titration of the concentration of the substance is also recommended before conducting the experiment. In the articles published by Xu et al. (2021a and 2021b) , ATP is supplemented in a concentration of 10 mM.…”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

“…In the articles published by Xu et al. (2021a and 2021b) , ATP is supplemented in a concentration of 10 mM.…”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

“…Assessment of the effect of ATP supplementation on the cellular signaling pathway by immunoblotting: Use ATP supplementation described in the published article ( Xu et al., 2021a , 2021b ) as examples. FX11 is a LDHA inhibitor that can effectively lower the intracellular ATP level so that phosphorylation of Akt and Foxo1 are compromised because the upstream PI3K’s activity is sensitive to the level of intracellular ATP.…”

Section: Expected Outcomesmentioning

confidence: 99%

“…This protocol, optimized for primary mouse T lymphocytes, describes steps for SLO-mediated cell membrane permeabilization and substance supplementation, followed by immunoblotting and immunofluorescent microscopy for assessing cellular effects. For complete details on the use and execution of this protocol, please refer to Xu et al., 2021a , Xu et al., 2021b .…”

mentioning

confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to Xu et al., 2021a , Xu et al., 2021b .…”

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confidence: 99%

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Delivery of membrane impermeable molecules to primary mouse T lymphocytes

2021

STAR Protocols

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Summary The pore-forming toxin streptolysin-O (SLO) enables intracellular delivery of molecules up to 100 kDa and has been used for short-term delivery of membrane-impermeable substances to assess their effects on cellular activities. A limitation of this technique is the loss of intracellular components and the potential unpredicted alterations of cellular metabolism and signaling. This protocol, optimized for primary mouse T lymphocytes, describes steps for SLO-mediated cell membrane permeabilization and substance supplementation, followed by immunoblotting and immunofluorescent microscopy for assessing cellular effects. For complete details on the use and execution of this protocol, please refer to Xu et al., 2021a , Xu et al., 2021b .

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Section: Step-by-step Methods Detailsmentioning

confidence: 99%

“…In the articles published by Xu et al. (2021a and 2021b) , ATP is supplemented in a concentration of 10 mM.…”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

Section: Expected Outcomesmentioning

confidence: 99%

mentioning

confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to Xu et al., 2021a , Xu et al., 2021b .…”

mentioning

confidence: 99%

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Delivery of membrane impermeable molecules to primary mouse T lymphocytes

2021

STAR Protocols

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Principles of PI 3K Biology and Its Role in Lymphoma

Madsen¹

2023

Precision Cancer Therapies, Volume 1 ‐ Targeting Oncogenic Drivers and Signaling Pathways in Lymphoid Malignancies

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Hsp90 Promotes Gastric Cancer Cell Metastasis and Stemness by Regulating the Regional Distribution of Glycolysis‐Related Metabolic Enzymes in the Cytoplasm

Liu,

Shen,

Zhou

et al. 2024

Advanced Science

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Heat‐shock protein 90 (Hsp90) plays a crucial role in tumorigenesis and tumor progression; however, its mechanism of action in gastric cancer (GC) remains unclear. Here, the role of Hsp90 in GC metabolism is the focus of this research. High expression of Hsp90 in GC tissues can interact with glycolysis, collectively affecting prognosis in clinical samples. Both in vitro and in vivo experiments demonstrate that Hsp90 is able to regulate the migration and stemness properties of GC cells. Metabolic phenotype analyses indicate that Hsp90 influences glycolytic metabolism. Mechanistically, Hsp90 interacts with glycolysis‐related enzymes, forming multienzyme complexes to enhance glycolysis efficiency and yield. Additionally, Hsp90 binds to cytoskeleton‐related proteins, regulating the regional distribution of glycolytic enzymes at the cell margin and lamellar pseudopods. This effect could lead to a local increase in efficient energy supply from glycolysis, further promoting epithelial‐mesenchymal transition (EMT) and metastasis. In summary, Hsp90, through its interaction with metabolic enzymes related to glycolysis, forms multi‐enzyme complexes and regulates regional distribution of glycolysis by dynamic cytoskeletal adjustments, thereby promoting the migration and stemness of GC cells. These conclusions also support the potential for a combined targeted approach involving Hsp90, glycolysis, and the cytoskeleton in clinical therapy.

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Glycolytic ATP fuels phosphoinositide 3-kinase signaling to support effector T helper 17 cell responses

Cited by 69 publications

References 66 publications

Delivery of membrane impermeable molecules to primary mouse T lymphocytes

Delivery of membrane impermeable molecules to primary mouse T lymphocytes

Principles of PI 3K Biology and Its Role in Lymphoma

Hsp90 Promotes Gastric Cancer Cell Metastasis and Stemness by Regulating the Regional Distribution of Glycolysis‐Related Metabolic Enzymes in the Cytoplasm

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