Regulation of the energy sensor AMP-activated protein kinase by antigen receptor and Ca2+ in T lymphocytes
Open accessAbstract
The adenosine monophosphate (AMP)–activated protein kinase (AMPK) has a crucial role in maintaining cellular energy homeostasis. This study shows that human and mouse T lymphocytes express AMPKα1 and that this is rapidly activated in response to triggering of the T cell antigen receptor (TCR). TCR stimulation of AMPK was dependent on the adaptors LAT and SLP76 and could be mimicked by the elevation of intracellular Ca2+ with Ca2+ ionophores or thapsigargin. AMPK activation was also induced by energy stress and depletion of cellular adenosine triphosphate (ATP). However, TCR and Ca2+ stimulation of AMPK required the activity of Ca2+–calmodulin-dependent protein kinase kinases (CaMKKs), whereas AMPK activation induced by increased AMP/ATP ratios did not. These experiments reveal two distinct pathways for the regulation of AMPK in T lymphocytes. The role of AMPK is to promote ATP conservation and production. The rapid activation of AMPK in response to Ca2+ signaling in T lymphocytes thus reveals that TCR triggering is linked to an evolutionally conserved serine kinase that regulates energy metabolism. Moreover, AMPK does not just react to cellular energy depletion but also anticipates it.
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Lymphocytes exclusively express the a1 catalytic subunit of AMPK.
“Lymphocytes exclusively express the a1 catalytic subunit of AMPK (87), and TCR stimulation promotes LKB1-dependent AMPK activation in lymphocytes (87, 88).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [87]
TCR stimulation promotes LKB1-dependent AMPK activation in lymphocytes.
“Lymphocytes exclusively express the a1 catalytic subunit of AMPK (87), and TCR stimulation promotes LKB1-dependent AMPK activation in lymphocytes (87, 88).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [87]
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- Authors
- Tamás, P., Hawley, S. A., Clarke, R. G., Mustard, K. J., Green, K., Hardie, D. G., & Cantrell, D. A.
- Affiliations
- 1Division of Cell Biology and Immunology
- University of Dundee (GB)
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2006-07-03
- Volume
- 203
- Issue
- 7
- Pages
- 1665-1670
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2118355
- OpenAlex
- W2159903725
- Cited by
- 328
- References
- 30
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 12 · 2023: 14 · 2022: 13 · 2021: 19 · 2020: 18 · 2019: 13 · 2018: 19 · 2017: 24 · 2016: 18 · 2015: 21 · 2014: 18 · 2013: 21 · 2012: 25
- FWCI
- 6.71
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion, other-oa)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- AMPK, T cells, T cell receptor signaling, calcium signaling, CaMKK, energy homeostasis, LAT, SLP-76, ATP depletion, AMP/ATP ratio, energy metabolism, thapsigargin, calcium ionophore
- MeSH terms
- Animals, Benzimidazoles, Calcium, Cells, Cultured, Energy Metabolism, Enzyme Inhibitors, Humans, Isoquinolines, Mice, Inbred C57BL, Multienzyme Complexes, Receptors, Antigen, T-Cell, T-Lymphocytes, Protein Serine-Threonine Kinases, Jurkat Cells, Mice, Naphthalimides, AMP-Activated Protein Kinases
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