Differential AMP-activated Protein Kinase (AMPK) Recognition mechanism of Ca2+/calmodulin-dependent protein kinase kinase isoforms
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Ca(2+)/calmodulin-dependent protein kinase kinase β (CaMKKβ) is a known activating kinase for AMP-activated protein kinase (AMPK). In vitro, CaMKKβ phosphorylates Thr(172) in the AMPKα subunit more efficiently than CaMKKα, with a lower Km (∼2 μm) for AMPK, whereas the CaMKIα phosphorylation efficiencies by both CaMKKs are indistinguishable. Here we found that subdomain VIII of CaMKK is involved in the discrimination of AMPK as a native substrate by measuring the activities of various CaMKKα/CaMKKβ chimera mutants. Site-directed mutagenesis analysis revealed that Leu(358) in CaMKKβ/Ile(322) in CaMKKα confer, at least in part, a distinct recognition of AMPK but not of CaMKIα.
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LKB1 and CAMKK2 are the two main mammalian upstream molecules that phosphorylate AMPK.
“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 [33]
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- Authors
- Fujiwara, Y., Kawaguchi, Y., Fujimoto, T., Kanayama, N., Magari, M., & Tokumitsu, H.
- Affiliations
- Okayama University (JP)
- Carna Biosciences (Japan) (JP)
- Corresponding author
- Tokumitsu, Hiroshi
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 291
- Issue
- 26
- Pages
- 13802-13808
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC4919462
- OpenAlex
- W2468561626
- Cited by
- 40
- References
- 31
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 6 · 2023: 5 · 2022: 4 · 2021: 8 · 2020: 4 · 2019: 2 · 2018: 3 · 2017: 2
- FWCI
- 1.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (26440056)
- 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 › PI3K/AKT/mTOR signaling in cancer
- Keywords
- AMPK, CaMKKβ, kinase substrate recognition, substrate discrimination, calcium/calmodulin-dependent protein kinase
- MeSH terms
- Animals, Enzyme Activation, Humans, Mutagenesis, Site-Directed, Amino Acid Substitution, Cell Line, Tumor, Rats, Calcium-Calmodulin-Dependent Protein Kinase Kinase, AMP-Activated Protein Kinases
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