PMID- 10187789
OWN - NLM
STAT- MEDLINE
DCOM- 19990503
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 15
DP  - 1999 Apr 9
TI  - Inhibition of the Ca2+/calmodulin-dependent protein kinase I cascade by
      cAMP-dependent protein kinase.
PG  - 10086-93
AB  - Several recent studies have shown that Ca2+/calmodulin-dependent protein kinase I
      (CaMKI) is phosphorylated and activated by a protein kinase (CaMKK) that is
      itself subject to regulation by Ca2+/calmodulin. In the present study, we
      demonstrate that this enzyme cascade is regulated by cAMP-mediated activation of 
      cAMP-dependent protein kinase (PKA). In vitro, CaMKK is phosphorylated by PKA and
      this is associated with inhibition of enzyme activity. The major site of
      phosphorylation is threonine 108, although additional sites are phosphorylated
      with lower efficiency. In vitro, CaMKK is also phosphorylated by CaMKI at the
      same sites as PKA, suggesting that this regulatory phosphorylation might play a
      role as a negative-feedback mechanism. In intact PC12 cells, activation of PKA
      with forskolin resulted in a rapid inhibition of both CaMKK and CaMKI activity.
      In hippocampal slices CaMKK was phosphorylated under basal conditions, and
      activation of PKA led to an increase in phosphorylation. Two-dimensional
      phosphopeptide mapping indicated that activation of PKA led to increased
      phosphorylation of multiple sites including threonine 108. These results indicate
      that in vitro and in intact cells the CaMKK/CaMKI cascade is subject to
      inhibition by PKA-mediated phosphorylation of CaMKK. The phosphorylation and
      inhibition of CaMKK by PKA is likely to be involved in modulating the balance
      between cAMP- and Ca2+-dependent signal transduction pathways.
FAU - Matsushita, M
AU  - Matsushita M
AD  - Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University,
      New York, New York 10021, USA.
FAU - Nairn, A C
AU  - Nairn AC
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Kinase)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 1)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 4)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.17 (Camk1 protein, rat)
RN  - EC 2.7.11.17 (Camk4 protein, rat)
RN  - EC 2.7.11.17 (Pnck protein, rat)
SB  - IM
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinase Kinase
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 1
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 4
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*antagonists &
      inhibitors/*metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/*metabolism
MH  - Feedback
MH  - Hippocampus/enzymology/metabolism
MH  - PC12 Cells
MH  - Peptide Mapping
MH  - Phosphorylation
MH  - Protein-Serine-Threonine Kinases/metabolism
MH  - Rats
MH  - Substrate Specificity
EDAT- 1999/04/03 00:00
MHDA- 1999/04/03 00:01
CRDT- 1999/04/03 00:00
PHST- 1999/04/03 00:00 [pubmed]
PHST- 1999/04/03 00:01 [medline]
PHST- 1999/04/03 00:00 [entrez]
AID - 10.1074/jbc.274.15.10086 [doi]
AID - S0021-9258(19)73687-4 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Apr 9;274(15):10086-93. doi: 10.1074/jbc.274.15.10086.