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The Sedoheptulose Kinase CARKL Directs Macrophage Polarization through Control of Glucose Metabolism
Open accessAbstract
Immune cells are somewhat unique in that activation responses can alter quantitative phenotypes upwards of 100,000-fold. To date little is known about the metabolic adaptations necessary to mount such dramatic phenotypic shifts. Screening for novel regulators of macrophage activation, we found nonprotein kinases of glucose metabolism among the most enriched classes of candidate immune modulators. We find that one of these, the carbohydrate kinase-like protein CARKL, is rapidly downregulated in vitro and in vivo upon LPS stimulation in both mice and humans. Interestingly, CARKL catalyzes an orphan reaction in the pentose phosphate pathway, refocusing cellular metabolism to a high-redox state upon physiological or artificial downregulation. We find that CARKL-dependent metabolic reprogramming is required for proper M1- and M2-like macrophage polarization and uncover a rate-limiting requirement for appropriate glucose flux in macrophage polarization.
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“TCR/CD28 stimulation of T cells (6), the stimulation of surface immunoglobulin on B cells (41), and TLR stimulation of macrophages and dendritic cells (DCs) (42, 43) all promote changes in aerobic glycolysis characteristic of the Warburg effect.”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [43]
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Cites
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009) · Science · doi:10.1126/science.1160809 · Cited by 16,197
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425
Alternative activation of macrophages: mechanism and functions
Gordon, S., & Martinez, F. O. (2010) · Immunity · doi:10.1016/j.immuni.2010.05.007 · Cited by 4,197
Approaching the asymptote? Evolution and revolution in immunology.Preprint
Janeway, C. (1989) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1989.054.01.003 · Cited by 3,396
The Inflammasomes: Guardians of the Body
Martinon, F., Mayor, A., & Tschopp, J. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132715 · Cited by 2,436
Nathan, C., & Ding, A. (2010) · Cell · doi:10.1016/j.cell.2010.02.029 · Cited by 2,183
Inflammation 2010: New Adventures of an Old Flame
Medzhitov, R. M. (2010) · Cell · doi:10.1016/j.cell.2010.03.006 · Cited by 1,928
Shi, L. Z., Wang, R., Huang, G., Vogel, P., Neale, G., Green, D. R., & Chi, H. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20110278 · Cited by 1,803
SOCS proteins, cytokine signalling and immune regulation
Yoshimura, A., Naka, T., & Kubo, M. (2007) · Nature Reviews Immunology · doi:10.1038/nri2093 · Cited by 1,580
Toll-like receptor–induced changes in glycolytic metabolism regulate dendritic cell activation
Krawczyk, C. M., Holowka, T., Sun, J., Blagih, J., Amiel, E., DeBerardinis, R. J., Cross, J. R., Jung, E., Thompson, C. B., Jones, R. G., et al. (2010) · Blood · doi:10.1182/blood-2009-10-249540 · Cited by 1,246
ModBase, a database of annotated comparative protein structure models, and associated resources
Pieper, U., Webb, B., Barkan, D. T., Schneidman‐Duhovny, D., Schlessinger, A., Braberg, H., Yang, Z., Meng, E., Pettersen, E. F., Huang, C. C., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq1091 · Cited by 1,073
The Inflammatory Response to Cell Death
Rock, K. L., & Kono, H. (2007) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathmechdis.3.121806.151456 · Cited by 979
Fuel feeds function: energy metabolism and the T-cell response
Fox, C. J., Hammerman, P. S., & Thompson, C. B. (2005) · Nature reviews. Immunology · doi:10.1038/nri1710 · Cited by 841
Cytokine Signaling Modules in Inflammatory Responses
O’Shea, J. J., & Murray, P. J. (2008) · Immunity · doi:10.1016/j.immuni.2008.03.002 · Cited by 833
The power to reduce: pyridine nucleotides—small molecules with a multitude of functions
Pollak, N., Dölle, C., & Ziegler, M. (2007) · Biochemical Journal · doi:10.1042/bj20061638 · Cited by 730
p53 regulates glucose metabolism through an IKK-NF-κB pathway and inhibits cell transformation
Kawauchi, K., Araki, K., Tobiume, K., & Tanaka, N. (2008) · Nature Cell Biology · doi:10.1038/ncb1724 · Cited by 660
Modulation of transcription factor NF-kappa B binding activity by oxidation-reduction in vitro.
Toledano, M. B., & Leonard, W. J. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.10.4328 · Cited by 657
Kazama, H., Ricci, J.-E., Herndon, J. M., Hoppe, G., Green, D. R., & Ferguson, T. A. (2008) · Immunity · doi:10.1016/j.immuni.2008.05.013 · Cited by 627
Drapier, J., & Hibbs, J. B. (1988) · The Journal of Immunology · doi:10.4049/jimmunol.140.8.2829 · Cited by 592
Oliver, F. J., Murcia, J. M., Nacci, C., Decker, P., Andriantsitohaina, R., Muller, S., de la Rubia, G., Stoclet, J., & de MURCIA, G. (1999) · The EMBO Journal · doi:10.1093/emboj/18.16.4446 · Cited by 583
Tools for comparative protein structure modeling and analysis
Eswar, N. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg543 · Cited by 481
Murray, P. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500419102 · Cited by 395
Approaching the Asymptote: 20 Years Later
Medzhitov, R. M. (2009) · Immunity · doi:10.1016/j.immuni.2009.06.004 · Cited by 380
Metabolic costs of mounting an antigen-stimulated immune response in adult and aged C57BL/6J mice
Demas, G. E., Chefer, V. I., Talan, M. I., & Nelson, R. J. (1997) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1997.273.5.r1631 · Cited by 367
Ojaniemi, M., Glumoff, V., Harju, K., Vähä-Mäkilä, M., Vuori, K., & Hallman, M. (2003) · European Journal of Immunology · doi:10.1002/eji.200323376 · Cited by 324
KIM, C. S., Sano, Y., Todorova, K. A., Carlson, B. A., Arpa, L., Celada, A., Lawrence, T., Otsu, K., Brissette, J. L., Arthur, J. S. C., et al. (2008) · Nature Immunology · doi:10.1038/ni.1640 · Cited by 272
Self-citationLorenz, M. A., Burant, C., & Kennedy, R. T. (2011) · Analytical Chemistry · doi:10.1021/ac103313x · Cited by 240
Self-citationMetabolism, migration and memory in cytotoxic T cells
Finlay, D. K., & Cantrell, D. A. (2011) · Nature reviews. Immunology · doi:10.1038/nri2888 · Cited by 227
Whyte, C. S., Bishop, E., Rückerl, D., Gaspar-Pereira, S., Barker, R. N., Allen, J. E., Rees, A. J., & Wilson, H. M. (2011) · Journal of Leukocyte Biology · doi:10.1189/jlb.1110644 · Cited by 226
Kumar, S., Rabson, A. B., & Gélinas, C. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.7.3094 · Cited by 165
Role of phagocytosis in the activation of macrophages
Schnyder, J., & Baggiolini, M. (1978) · The Journal of Experimental Medicine · doi:10.1084/jem.148.6.1449 · Cited by 147
MODBASE, a database of annotated comparative protein structure models and associated resources
Pieper, U., Eswar, N., Webb, B., Eramian, D., Kelly, L., Barkan, D. T., Carter, H., Mankoo, P. K., Karchin, R., Martı́-Renom, M. A., et al. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn791 · Cited by 147
Clasquin, M. F., Melamud, E., Singer, A. U., Gooding, J. R., Xu, X., Dong, A., Cui, H., Campagna, S. R., Savchenko, A. V., Yakunin, A. F., et al. (2011) · Cell · doi:10.1016/j.cell.2011.05.022 · Cited by 121
The p38α Kinase Plays a Central Role In Inflammation
Schieven, G. L. (2009) · Current Topics in Medicinal Chemistry · doi:10.2174/156802609789630974 · Cited by 107
Wassenberg, J. J., Dezfulian, C., & Nicchitta, C. V. (1999) · Journal of Cell Science · doi:10.1242/jcs.112.13.2167 · Cited by 102
Salminen, A., Paimela, T., Suuronen, T., & Kaarniranta, K. (2008) · Immunology Letters · doi:10.1016/j.imlet.2007.12.017 · Cited by 99
Pellny, T. K., Locato, V., Díaz‐Vivancos, P., Marković, J., Gara, L. D., Pallardó, F. V., & Foyer, C. H. (2009) · Molecular Plant · doi:10.1093/mp/ssp008 · Cited by 89
Glycogen synthase kinase-3 is an early determinant in the differentiation of pathogenic Th17 cells
Beurel, E., Yeh, W.-I., Michalek, S. M., Harrington, L. E., & Jope, R. S. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003511 · Cited by 86
Metabolic Switches of T-Cell Activation and Apoptosis
Perl, A., Gergely, P., Puskas, F., & Banki, K. (2002) · Antioxidants and Redox Signaling · doi:10.1089/15230860260196227 · Cited by 82
Kim, B.-C., Jeon, W.-K., Hong, H.-Y., Jeon, K. B., Hahn, J.-H., Kim, Y., Numazawa, S., Yosida, T., Park, E., & Lim, C. (2007) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2007.05.032 · Cited by 73
Spolarics, Z., & Wu, J. (1997) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1997.273.6.g1304 · Cited by 68
Cross-Regulation of Carbon Monoxide and the Adenosine A2a Receptor in Macrophages
Haschemi, A., Wagner, O. F., Marculescu, R., Wegiel, B., Robson, S. C., Gagliani, N., Gallo, D. J., Chen, J., Bach, F. H., & Otterbein, L. E. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.9.5921 · Cited by 50
Self-citationWamelink, M. M. C., Struys, E. A., Jansen, E. E. W., Levtchenko, E. N., Zijlstra, F., Engelke, U. F. H., Blom, H. J., Jakobs, C., & Wevers, R. A. (2008) · Human Mutation · doi:10.1002/humu.20685 · Cited by 46
Wang, F., Wang, L. Y., Wright, D. E., & Parmely, M. J. (1999) · Infection and Immunity · doi:10.1128/iai.67.10.5409-5416.1999 · Cited by 40
Park, J.-H., Hu, Y., Murthy, T. V., Vannberg, F. O., Shen, B., Rolfs, A., Hutti, J. E., Cantley, L. C., LaBaer, J., Harlow, E., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503141102 · Cited by 38
Self-citationEffect of indomethacin on clinical progress and renal function in cystinosis.
Haycock, G. B., Al-Dahhan, J., MAK, R. H. K., & CHANTLER, C. (1982) · Archives of Disease in Childhood · doi:10.1136/adc.57.12.934 · Cited by 37
Kardon, T., Stroobant, V., Veiga‐da‐Cunha, M., & SCHAFTINGEN, E. V. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.08.024 · Cited by 29
Marsik, C. L., Sunder‐Plaßmann, R., Jilma, B., Kovar, F. M., Mannhalter, C., Wagner, O. F., Rumpold, H., & Endler, G. (2006) · Clinical Chemistry · doi:10.1373/clinchem.2006.069823 · Cited by 27
Self-citationChen, Y.-J., Hsu, K., Tsai, J., Hung, C.-H., Kuo, T.-C., & Chen, Y.-L. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.07.002 · Cited by 14
Kuttner, R. E., SCHUMER, W., & Apantaku, F. O. (1982) · PubMed · Cited by 7
Formation of an Unusual Secondary Sedoheptulose Phosphate by Hexokinase-Mediated Phosphorylation
Schmidt, U., Stiller, R., Brade, H., & Thiem, J. (1998) · Synlett · doi:10.1055/s-1998-1586 · Cited by 7
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- Warburg, 1924, Ueber den Stoffwechsel der Tumoren, Biochem. Z., 152, 319
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O'Neill, L. A. J., Kishton, R. J., & Rathmell, J. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.70 · Cited by 3,315
Murray, P. J. (2017) · Annual Review of Physiology · doi:10.1146/annurev-physiol-022516-034339 · Cited by 2,981
Microglial M1/M2 polarization and metabolic states
Orihuela, R., McPherson, C. A., & Harry, G. J. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13139 · Cited by 2,070
Jha, A. K., Huang, S. C.-C., Sergushichev, A., Lampropoulou, V., Ivanova, Y., Loginicheva, E., Chmielewski, K., Stewart, K. M., Ashall, J., Everts, B., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.02.005 · Cited by 2,066
The metabolic signature of macrophage responses
Viola, A., Munari, F., Sánchez-Rodríguez, R., Scolaro, T., & Castegna, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01462 · Cited by 2,021
Metadata
- Authors
- Haschemi, A., Kosma, P., Gille, L., Evans, C. R., Burant, C. F., Starkl, P., Knapp, B., Haas, R., Schmid, J. A., Jandl, C., Amir, S., Lubec, G., Park, J., Esterbauer, H., Bilban, M., Brizuela, L., Pospisilik, J. A., Otterbein, L. E., & Wagner, O.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- BOKU University (AT)
- University of Veterinary Medicine Vienna (AT)
- University of Michigan (US)
- Medical University of Vienna (AT)
- Harvard University (US)
- Max Planck Institute of Immunobiology and Epigenetics (DE)
- Corresponding author
- Haschemi, Arvand
- Pospisilik, J. Andrew
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 15
- Issue
- 6
- Pages
- 813-826
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3370649
- OpenAlex
- W2047563937
- Cited by
- 635
- References
- 53
- Citations by year
- 2026: 30 · 2025: 35 · 2024: 68 · 2023: 56 · 2022: 41 · 2021: 60 · 2020: 57 · 2019: 50 · 2018: 48 · 2017: 61 · 2016: 35 · 2015: 41 · 2014: 24 · 2013: 14 · 2012: 3
- FWCI
- 11.47
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Bundesministerium für Wissenschaft und Forschung
- National Institute of General Medical Sciences (R01GM088666)
- National Institute of Diabetes and Digestive and Kidney Diseases (K25DK092558, DK089503, P30DK089503)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- macrophage polarization, glucose metabolism, pentose phosphate pathway, metabolic reprogramming, M1/M2 macrophages, lipopolysaccharide stimulation, redox state, immune cell metabolism
- MeSH terms
- Amino Acid Sequence, Animals, Cell Line, Double-Blind Method, Energy Metabolism, Glucose, Humans, Lipopolysaccharides, Macrophages, Male, Mice, Inbred C57BL, Models, Molecular, Phenotype, Receptors, Immunologic, Transcription Factors, Tumor Necrosis Factor-alpha, Down-Regulation, Interleukin-6, Gene Expression Regulation, Enzymologic, Cell Polarity, Protein Structure, Tertiary, Phosphotransferases (Alcohol Group Acceptor), Endotoxemia, Carbohydrate Metabolism, Mice
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