Ca 2+/calmodulin-dependent protein kinase kinase beta is regulated by multisite phosphorylation
Journal article
Green, Michelle, Scott, John, Steel, Rohan, Oakhill, Jonathan, Kemp, Bruce and Means, Anthony. (2011). Ca 2+/calmodulin-dependent protein kinase kinase beta is regulated by multisite phosphorylation. Journal of Biological Chemistry. 286(32), pp. 28066 - 28079. https://doi.org/10.1074/jbc.M111.251504
Authors | Green, Michelle, Scott, John, Steel, Rohan, Oakhill, Jonathan, Kemp, Bruce and Means, Anthony |
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Abstract | Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) is a serine/threonine-directed kinase that is activated following increases in intracellular Ca2+. CaMKKβ activates Ca2+/calmodulin-dependent protein kinase I, Ca2+/calmodulin-dependent protein kinase IV, and the AMP-dependent protein kinase in a number of physiological pathways, including learning and memory formation, neuronal differentiation, and regulation of energy balance. Here, we report the novel regulation of CaMKKβ activity by multisite phosphorylation. We identify three phosphorylation sites in the N terminus of CaMKKβ, which regulate its Ca2+/calmodulin-independent autonomous activity. We then identify the kinases responsible for these phosphorylations as cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase 3 (GSK3). In addition to regulation of autonomous activity, we find that phosphorylation of CaMKKβ regulates its half-life. We find that cellular levels of CaMKKβ correlate with CDK5 activity and are regulated developmentally in neurons. Finally, we demonstrate that appropriate phosphorylation of CaMKKβ is critical for its role in neurite development. These results reveal a novel regulatory mechanism for CaMKKβ-dependent signaling cascades. |
Year | 2011 |
Journal | Journal of Biological Chemistry |
Journal citation | 286 (32), pp. 28066 - 28079 |
ISSN | 0021-9258 |
Digital Object Identifier (DOI) | https://doi.org/10.1074/jbc.M111.251504 |
Open access | Open access |
Page range | 28066 - 28079 |
Publisher's version |
https://acuresearchbank.acu.edu.au/item/88927/ca-2-calmodulin-dependent-protein-kinase-kinase-beta-is-regulated-by-multisite-phosphorylation
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