PMID- 10022832
OWN - NLM
STAT- MEDLINE
DCOM- 19990426
LR  - 20181113
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 4
DP  - 1999 Feb 15
TI  - The MAP kinase ERK2 inhibits the cyclic AMP-specific phosphodiesterase HSPDE4D3
      by phosphorylating it at Ser579.
PG  - 893-903
AB  - The extracellular receptor stimulated kinase ERK2 (p42(MAPK))-phosphorylated
      human cAMP-specific phosphodiesterase PDE4D3 at Ser579 and profoundly reduced (
      approximately 75%) its activity. These effects could be reversed by the action of
      protein phosphatase PP1. The inhibitory state of PDE4D3, engendered by ERK2
      phosphorylation, was mimicked by the Ser579-->Asp mutant form of PDE4D3. In COS1 
      cells transfected to express PDE4D3, challenge with epidermal growth factor (EGF)
      caused the phosphorylation and inhibition of PDE4D3. This effect was blocked by
      the MEK inhibitor PD98059 and was not apparent using the Ser579-->Ala mutant form
      of PDE4D3. Challenge of HEK293 and F442A cells with EGF led to the
      PD98059-ablatable inhibition of endogenous PDE4D3 and PDE4D5 activities. EGF
      challenge of COS1 cells transfected to express PDE4D3 increased cAMP levels
      through a process ablated by PD98059. The activity of the Ser579-->Asp mutant
      form of PDE4D3 was increased by PKA phosphorylation. The transient form of the
      EGF-induced inhibition of PDE4D3 is thus suggested to be due to feedback
      regulation by PKA causing the ablation of the ERK2-induced inhibition of PDE4D3. 
      We identify a novel means of cross-talk between the cAMP and ERK signalling
      pathways whereby cell stimuli that lead to ERK2 activation may modulate cAMP
      signalling.
FAU - Hoffmann, R
AU  - Hoffmann R
AD  - Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology,
      Davidson and Wolfson Buildings, IBLS, University of Glasgow, Glasgow G12 8QQ, UK.
FAU - Baillie, G S
AU  - Baillie GS
FAU - MacKenzie, S J
AU  - MacKenzie SJ
FAU - Yarwood, S J
AU  - Yarwood SJ
FAU - Houslay, M D
AU  - Houslay MD
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Flavonoids)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.4.17 (3',5'-Cyclic-AMP Phosphodiesterases)
RN  - EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - 3',5'-Cyclic-AMP Phosphodiesterases/genetics/*metabolism
MH  - Animals
MH  - COS Cells
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cyclic AMP/*metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - Cyclic Nucleotide Phosphodiesterases, Type 4
MH  - Enzyme Activation
MH  - Epidermal Growth Factor/pharmacology
MH  - Flavonoids/pharmacology
MH  - Humans
MH  - Mitogen-Activated Protein Kinase 1
MH  - Mutation
MH  - Phosphoprotein Phosphatases/antagonists & inhibitors/metabolism
MH  - Phosphorylation
MH  - Signal Transduction
MH  - Transfection/genetics
PMC - PMC1171182
EDAT- 1999/02/18 00:00
MHDA- 1999/02/18 00:01
CRDT- 1999/02/18 00:00
PHST- 1999/02/18 00:00 [pubmed]
PHST- 1999/02/18 00:01 [medline]
PHST- 1999/02/18 00:00 [entrez]
AID - 10.1093/emboj/18.4.893 [doi]
PST - ppublish
SO  - EMBO J. 1999 Feb 15;18(4):893-903. doi: 10.1093/emboj/18.4.893.