title: Differential AMP-activated Protein Kinase (AMPK) Recognition Mechanism of Ca2+/Calmodulin-dependent Protein Kinase Kinase Isoforms.
abstract: 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.
authors.affiliation: From the Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan and.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: From the Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan and.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kawaguchi
authors.affiliation: Carna Biosciences, Inc., Kobe 650-0047, Japan.
authors.forename: Tomohito
authors.initials: T
authors.lastname: Fujimoto
authors.affiliation: From the Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan and.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kanayama
authors.affiliation: From the Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan and.
authors.forename: Masaki
authors.initials: M
authors.lastname: Magari
authors.affiliation: From the Division of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan and tokumit@okayama-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tokumitsu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D019943:Amino Acid Substitution; D000818:Animals; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D016297:Mutagenesis, Site-Directed; D051381:Rats
chemical_list: C517695:CAMKK1 protein, human; C517698:CAMKK2 protein, human; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; C517701:Camkk1 protein, rat; C517702:Camkk2 protein, rat; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated kinase (AMPK); Ca2+/calmodulin-dependent protein kinase (CaMK); CaMKI; CaMKK; calmodulin (CaM); phosphorylation; substrate recognition; substrate specificity