The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
5′-AMP Activates the AMP-activated Protein Kinase Cascade, and Ca2+/Calmodulin Activates the Calmodulin-dependent Protein Kinase I Cascade, via Three Independent Mechanisms
Open accessAbstract
AMP-activated protein kinase (AMPK) and Ca2+/calmodulin (CaM)-dependent protein kinase I (CaMKI) are protein kinases that are regulated both by allosteric activation (AMP and Ca2+/CaM, respectively) and by phosphorylation by upstream protein kinases (AMPK kinase (AMPKK) and CaMKI kinase (CaMKIK), respectively). We now report that AMPKK can activate CaMKI and that, conversely, CaMKIK can activate AMPK. CaMKIK is 68-fold more effective at activating CaMKI than AMPK, while AMPKK is 17-fold more effective at activating AMPK than CaMKI. Our results suggest that CaMKIK and AMPKK are distinct enzymes dedicated to their respective kinase targets but with some overlap in their substrate specificities. The availability of alternative substrates for AMPKK and CaMKIK allowed the unequivocal demonstration that AMP and Ca2+/calmodulin promote the activation of AMPK and Ca2+/calmodulin promote the activation of AMPK and CaMKI, respectively, via three independent mechanisms: 1) direct activation of AMPK and CaMKI, 2) activation of AMPKK and CaMKIK, and 3) by binding to AMPK and CaMKI, inducing exposure of their phosphorylation sites. Since AMP and Ca2+/calmodulin each has a triple effect in its respective system, in vivo, the two systems would be expected to be exquisitely sensitive to changes in concentration of their respective activating ligands.
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Hanson, P. I., Meyer, T., Stryer, L., & Schulman, H. (1994) · Neuron · doi:10.1016/0896-6273(94)90306-9 · Cited by 500
Cited by
AMPK: a nutrient and energy sensor that maintains energy homeostasis
Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3311 · Cited by 4,602
Self-citationKahn, B. B., Alquier, T., Carling, D., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2004.12.003 · Cited by 2,799
Self-citationShaw, R. J., Kosmatka, M., Bardeesy, N., Hurley, R. L., Witters, L. A., DePinho, R. A., & Cantley, L. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308061100 · Cited by 1,797
LKB1 is the upstream kinase in the AMP-activated protein kinase cascade
Woods, A., Johnstone, S. R., Dickerson, K., Leiper, F. C., Fryer, L. G. D., Neumann, D., Schlattner, U., Wallimann, T., Carlson, M., & Carling, D. (2003) · Current Biology · doi:10.1016/j.cub.2003.10.031 · Cited by 1,650
Self-citationAMP-activated protein kinase: an energy sensor that regulates all aspects of cell function
Hardie, D. G. (2011) · Genes & Development · doi:10.1101/gad.17420111 · Cited by 1,638
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Metadata
- Authors
- Hawley, S. A., Selbert, M. A., Goldstein, E. G., Edelman, A. M., Carling, D., & Hardie, D. G.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1995-11
- Volume
- 270
- Issue
- 45
- Pages
- 27186-27191
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1974669825
- Cited by
- 440
- References
- 1
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: 5′-AMP Activates the AMP-activated Protein Kinase Cascade, and Ca2+/Calmodulin Activates the Calmodulin-dependent Protein Kinase I Cascade, via Three Independent Mechanisms. https://app.cochat.ai/papers/10.1074/jbc.270.45.27186
- The paper
- Hawley, S. A., Selbert, M. A., Goldstein, E. G., Edelman, A. M., Carling, D., & Hardie, D. G. (1995). 5′-AMP Activates the AMP-activated Protein Kinase Cascade, and Ca2+/Calmodulin Activates the Calmodulin-dependent Protein Kinase I Cascade, via Three Independent Mechanisms. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.270.45.27186
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