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

ABSTRACT: Ca(2+)/calmodulin-dependent protein kinase kinase ? (CaMKK?) is a known activating kinase for AMP-activated protein kinase (AMPK). In vitro, CaMKK? phosphorylates Thr(172) in the AMPK? subunit more efficiently than CaMKK?, with a lower Km (?2 ?m) for AMPK, whereas the CaMKI? 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 CaMKK?/CaMKK? chimera mutants. Site-directed mutagenesis analysis revealed that Leu(358) in CaMKK?/Ile(322) in CaMKK? confer, at least in part, a distinct recognition of AMPK but not of CaMKI?.

SUBMITTER: Fujiwara Y

PROVIDER: S-EPMC4919462 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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

Fujiwara Yuya Y Kawaguchi Yoshinori Y Fujimoto Tomohito T Kanayama Naoki N Magari Masaki M Tokumitsu Hiroshi H

The Journal of biological chemistry 20160505 26

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/CaMK ...[more]

PMID: 27151216

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