TY - JOUR
T1 - Differential AMP-activated protein kinase (AMPK) recognition mechanism of Ca2+/calmodulin-dependent protein kinase kinase isoforms
AU - Fujiwara, Yuya
AU - Kawaguchi, Yoshinori
AU - Fujimoto, Tomohito
AU - Kanayama, Naoki
AU - Magari, Masaki
AU - Tokumitsu, Hiroshi
N1 - Publisher Copyright:
© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2016/6/24
Y1 - 2016/6/24
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M116.727867
DO - 10.1074/jbc.M116.727867
M3 - Article
C2 - 27151216
AN - SCOPUS:84976339944
VL - 291
SP - 13802
EP - 13808
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 26
ER -