Enzymology
Differential AMP-activated Protein Kinase (AMPK) Recognition Mechanism of Ca2+/Calmodulin-dependent Protein Kinase Kinase Isoforms*
Differential AMPK Recognition of CaMKK Isoforms

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Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) is a known activating kinase for AMP-activated protein kinase (AMPK). In vitro, CaMKKβ phosphorylates Thr172 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 Leu358 in CaMKKβ/Ile322 in CaMKKα confer, at least in part, a distinct recognition of AMPK but not of CaMKIα.

AMP-activated kinase (AMPK)
Ca2+/calmodulin-dependent protein kinase (CaMK)
calmodulin (CaM)
phosphorylation
substrate specificity
CaMKI
CaMKK
substrate recognition

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*

This work was supported by Grant-in-aid for Scientific Research 26440056 (to H. T.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. The authors declare that they have no conflicts of interest with the contents of this article.

This article contains supplemental Fig. 1.