The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
LKB1 Is the Upstream Kinase in the AMP-Activated Protein Kinase Cascade
Open accessAbstract
Inactivating mutations in the protein kinase LKB1 lead to a dominantly inherited cancer in humans termed Peutz-Jeghers syndrome. The role of LKB1 is unclear, and only one target for LKB1 has been identified in vivo [3]. AMP-activated protein kinase (AMPK) is the downstream component of a protein kinase cascade that plays a pivotal role in energy homeostasis. AMPK may have a role in protecting the body from metabolic diseases including type 2 diabetes, obesity, and cardiac hypertrophy. We previously reported the identification of three protein kinases (Elm1, Pak1, and Tos3 [9]) that lie upstream of Snf1, the yeast homologue of AMPK. LKB1 shares sequence similarity with Elm1, Pak1, and Tos3, and we demonstrated that LKB1 phosphorylates AMPK on the activation loop threonine (Thr172) within the catalytic subunit and activates AMPK in vitro [9]. Here, we have investigated whether LKB1 corresponds to the major AMPKK activity present in cell extracts. AMPKK purified from rat liver corresponds to LKB1, and blocking LKB1 activity in cells abolishes AMPK activation in response to different stimuli. These results identify a link between two protein kinases, previously thought to lie in unrelated, distinct pathways, that are associated with human diseases.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Liver kinase B 1 (LKB1) [32] and calcium/calmodulin-dependent protein kinase kinase (CAMKK) 2 [33,34] can be employed as the two main mammalian upstream molecules that phosphorylate AMPK.”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [32]
Citations
Cites
Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652
Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase
Minokoshi, Y., Kim, Y.-B., Peroni, O. D., Fryer, L. G. D., Müller, C., Carling, D., & Kahn, B. B. (2002) · Nature · doi:10.1038/415339a · Cited by 2,053
Self-citationA serine/threonine kinase gene defective in Peutz–Jeghers syndrome
Hemminki, A., Markie, D., Tomlinson, I. P. M., Avizienyte, E., Roth, S., Loukola, A., Bignell, G. R., Warren, W., Aminoff, M., Höglund, P., et al. (1998) · Nature · doi:10.1038/34432 · Cited by 1,680
THE AMP-ACTIVATED/SNF1 PROTEIN KINASE SUBFAMILY: Metabolic Sensors of the Eukaryotic Cell?
Hardie, D. G., Carling, D., & Carlson, M. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.821 · Cited by 1,440
Self-citationHawley, S. A., Davison, M., Woods, A., Davies, S. P., Beri, R. K., Carling, D., & Hardie, D. G. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.44.27879 · Cited by 1,264
Self-citationPeutz-Jeghers syndrome is caused by mutations in a novel serine threoninekinase
Jenne, D. E., Reomann, H., Nezu, J., Friedel, W., Loff, S., Jeschke, R., Müller, O., Back, W. E., & Zimmer, M. (1998) · Nature Genetics · doi:10.1038/ng0198-38 · Cited by 1,201
Fryer, L. G. D., Patel, A. P., & Carling, D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202489200 · Cited by 1,035
Self-citationAMP-activated protein kinase, a metabolic master switch: possible roles in Type 2 diabetes
Winder, W. W., & Hardie, D. G. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.277.1.e1 · Cited by 1,000
Characterization of AMP-activated protein kinase γ-subunit isoforms and their role in AMP binding
CHEUNG, P. C. F., SALT, I. P., DAVIES, S. P., HARDIE, D. G., & CARLING, D. (2000) · Biochemical Journal · doi:10.1042/bj3460659 · Cited by 637
Self-citationActivation of yeast Snf1 and mammalian AMP-activated protein kinase by upstream kinases
Hong, S. P., Leiper, F. C., Woods, A., Carling, D., & Carlson, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1533136100 · Cited by 617
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Winder, 1999, AMP-activated protein kinase, a metabolic master switch, Am. J. Physiol., 277, 1
Cited by
Sorted by citations
Items 1,001–1,001 of 1,001
Forskolin Increases cAMP Levels and Enhances Recombinant Antibody Production in CHO Cell Cultures
Yoon, C., Kim, D., Lim, J. H., & Lee, G. M. (2020) · Biotechnology Journal · doi:10.1002/biot.202000264 · Cited by 13
Metadata
- Authors
- Woods, A., Johnstone, S. R., Dickerson, K., Leiper, F. C., Fryer, L. G. D., Neumann, D., Schlattner, U., Wallimann, T., Carlson, M., & Carling, D.
- Affiliations
- Hammersmith Hospital (GB)
- ETH Zurich (CH)
- Columbia University (US)
- Corresponding author
- Carling, David
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2003-11
- Volume
- 13
- Issue
- 22
- Pages
- 2004-2008
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W1990278643
- Cited by
- 1,650
- References
- 24
- Citations by year
- 2026: 40 · 2025: 26 · 2024: 47 · 2023: 51 · 2022: 60 · 2021: 86 · 2020: 64 · 2019: 62 · 2018: 83 · 2017: 85 · 2016: 75 · 2015: 85 · 2014: 86 · 2013: 96 · 2012: 90
- FWCI
- 25.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3546 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (GM-34095)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- LKB1, AMPK, AMPK activation, upstream kinases, kinase cascade, Peutz-Jeghers syndrome, energy homeostasis, Snf1, PAK1, rat liver
- MeSH terms
- Animals, Chromatography, Ion Exchange, Enzyme Activation, Liver, Multienzyme Complexes, Precipitin Tests, Blotting, Western, Protein Serine-Threonine Kinases, Rats, AMP-Activated Protein Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review