PMID- 29391954
OWN - NLM
STAT- MEDLINE
DCOM- 20180904
LR  - 20181113
IS  - 1687-5443 (Electronic)
IS  - 2090-5904 (Print)
IS  - 1687-5443 (Linking)
VI  - 2017
DP  - 2017
TI  - Activation State-Dependent Substrate Gating in Ca(2+)/Calmodulin-Dependent 
      Protein Kinase II.
PG  - 9601046
LID - 10.1155/2017/9601046 [doi]
LID - 9601046
AB  - Calcium/calmodulin-dependent protein kinase II (CaMKII) is highly concentrated in 
      the brain where its activation by the Ca(2+) sensor CaM, multivalent structure, 
      and complex autoregulatory features make it an ideal translator of Ca(2+) signals 
      created by different patterns of neuronal activity. We provide direct evidence 
      that graded levels of kinase activity and extent of T(287) (T(286)alpha isoform) 
      autophosphorylation drive changes in catalytic output and substrate selectivity. 
      The catalytic domains of CaMKII phosphorylate purified PSDs much more effectively 
      when tethered together in the holoenzyme versus individual subunits. Using 
      multisubstrate SPOT arrays, high-affinity substrates are preferentially 
      phosphorylated with limited subunit activity per holoenzyme, whereas multiple 
      subunits or maximal subunit activation is required for intermediate- and 
      low-affinity, weak substrates, respectively. Using a monomeric form of CaMKII to 
      control T(287) autophosphorylation, we demonstrate that increased 
      Ca(2+)/CaM-dependent activity for all substrates tested, with the extent of weak, 
      low-affinity substrate phosphorylation governed by the extent of T(287) 
      autophosphorylation. Our data suggest T(287) autophosphorylation regulates 
      substrate gating, an intrinsic property of the catalytic domain, which is 
      amplified within the multivalent architecture of the CaMKII holoenzyme.
FAU - Johnson, D E
AU  - Johnson DE
AD  - Biochemistry and Molecular Biology, Stark Neuroscience Research Institute, 
      Indiana University School of Medicine, Indianapolis, IN 46202, USA.
FAU - Hudmon, A
AU  - Hudmon A
AUID- ORCID: 0000-0002-5039-6803
AD  - Biochemistry and Molecular Biology, Stark Neuroscience Research Institute, 
      Indiana University School of Medicine, Indianapolis, IN 46202, USA.
LA  - eng
GR  - R01 NS078171/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20171217
PL  - United States
TA  - Neural Plast
JT  - Neural plasticity
JID - 100883417
RN  - 0 (Isoenzymes)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
SB  - IM
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/*metabolism
MH  - *Catalytic Domain
MH  - Humans
MH  - Isoenzymes/metabolism
MH  - Phosphorylation
MH  - Post-Synaptic Density/enzymology
MH  - Protein Domains
MH  - Protein Structure, Tertiary
MH  - Substrate Specificity
PMC - PMC5748111
EDAT- 2018/02/03 06:00
MHDA- 2018/09/05 06:00
PMCR- 2017/12/17
CRDT- 2018/02/03 06:00
PHST- 2017/07/15 00:00 [received]
PHST- 2017/10/23 00:00 [accepted]
PHST- 2018/02/03 06:00 [entrez]
PHST- 2018/02/03 06:00 [pubmed]
PHST- 2018/09/05 06:00 [medline]
PHST- 2017/12/17 00:00 [pmc-release]
AID - 10.1155/2017/9601046 [doi]
PST - ppublish
SO  - Neural Plast. 2017;2017:9601046. doi: 10.1155/2017/9601046. Epub 2017 Dec 17.