PMID- 10187850
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  - Phosphorylation-mediated activation and translocation of the cyclic AMP-specific 
      phosphodiesterase PDE4D3 by cyclic AMP-dependent protein kinase and
      mitogen-activated protein kinases. A potential mechanism allowing for the
      coordinated regulation of PDE4D activity and targeting.
PG  - 10557-65
AB  - In this study, we describe a novel mechanism by which a protein kinase C
      (PKC)-mediated activation of the Raf-extracellular signal-regulated kinase kinase
      (MEK)-extracellular signal-regulated kinase (ERK) cascade regulates the activity 
      and membrane targeting of members of the cyclic AMP-specific phosphodiesterase D 
      family (PDE4D). Using a combination of pharmacological and biochemical
      approaches, we show that increases in intracellular cAMP cause a protein kinase
      A-mediated phosphorylation and activation of the two PDE4D variants expressed in 
      vascular smooth muscle cells, namely PDE4D3 and PDE4D5. In addition, we show that
      stimulation of PKC via the associated activation of the Raf-MEK-ERK cascade
      results in the phosphorylation and activation of PDE4D3 in these cells.
      Furthermore, our studies demonstrate that simultaneous activation of both the
      protein kinase A and PKC-Raf-MEK-ERK pathways allows for a coordinated activation
      of PDE4D3 and for the translocation of the particulate PDE4D3 to the cytosolic
      fraction of these cells. These data are presented and discussed in the context of
      the activation of the Raf-MEK-ERK cascade acting to modulate the activation and
      subcellular targeting of PDE4D gene products mediated by cAMP.
FAU - Liu, H
AU  - Liu H
AD  - Department of Pharmacology & Toxicology, Queen's University, Kingston, Ontario
      K7L 3N6, Canada.
FAU - Maurice, D H
AU  - Maurice DH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Enzyme Inhibitors)
RN  - 11128-99-7 (Angiotensin II)
RN  - 1F7A44V6OU (Colforsin)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 3.1.4.17 (3',5'-Cyclic-AMP Phosphodiesterases)
RN  - EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - 3',5'-Cyclic-AMP Phosphodiesterases/*metabolism
MH  - Angiotensin II/pharmacology
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cells, Cultured
MH  - Colforsin/pharmacology
MH  - Cyclic AMP-Dependent Protein Kinases/*metabolism
MH  - Cyclic Nucleotide Phosphodiesterases, Type 4
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Muscle, Smooth, Vascular/enzymology
MH  - Phosphorylation
MH  - Protein Kinase C/metabolism
MH  - Rats
MH  - Tetradecanoylphorbol Acetate/pharmacology
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.274.15.10557 [doi]
AID - S0021-9258(19)73748-X [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Apr 9;274(15):10557-65. doi: 10.1074/jbc.274.15.10557.