PMID- 20196770
OWN - NLM
STAT- MEDLINE
DCOM- 20100614
LR  - 20191210
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 428
IP  - 1
DP  - 2010 Apr 28
TI  - Selective SUMO modification of cAMP-specific phosphodiesterase-4D5 (PDE4D5) 
      regulates the functional consequences of phosphorylation by PKA and ERK.
PG  - 55-65
LID - 10.1042/BJ20091672 [doi]
AB  - Enzymes from the PDE (phosphodiesterase) 4 cAMP-specific PDE family are crucial 
      for the maintenance of compartmentalized cAMP responses in many cell types. 
      Regulation of PDE activity can be achieved via post-translational modification 
      such as phosphorylation by ERK (extracellular-signal-regulated kinase) MAPKs 
      (mitogen-activated protein kinases) and PKA (protein kinase A). In the present 
      paper, we report for the first time that PDE4 isoforms from the PDE4A and PDE4D 
      subfamilies can be selectively modified by SUMO (small ubiquitin-related 
      modifier). We have identified a single SUMO site within a consensus tetrapeptide 
      motif, PsiKXE (where Psi represents a hydrophobic residue), which lies in the 
      catalytic unit of these enzymes. SUMO modification of PDE4 at this site was 
      observed upon overexpression of the SUMO E3 ligase PIASy [protein inhibitor of 
      activated STAT (signal transducer and activator of transcription) Y] in HEK 
      (human embryonic kidney)-293 cells and we identify PIASy as a novel binding 
      partner for long PDE4 isoforms. Site-directed mutagenesis of the acceptor lysine 
      residue ablated conjugation of PDE4 with SUMO, suggesting the presence of a 
      single SUMO site in the first subdomain of the conserved PDE4 catalytic unit. 
      This observation was supported by both cell-free in vitro SUMOylation assays and 
      analysis of SUMOylated spot-immobilized peptide arrays. SUMO modification of long 
      PDE4 isoforms serves to augment their activation by PKA phosphorylation and 
      repress their inhibition by ERK phosphorylation. Following ligation of 
      beta-adrenergic receptors, SUMOylation of PDE4 isoforms sufficiently amplified 
      PKA-stimulated PDE4 activity to reduce markedly the PKA phosphorylation status of 
      the beta2-adrenergic receptor. These results highlight a new means whereby cells 
      might achieve the selective regulation of the activity of cAMP-specific PDE4 
      enyzmes.
FAU - Li, Xiang
AU  - Li X
AD  - Neuroscience and Molecular Pharmacology, Division of Integrative Biology, IBLS, 
      Wolfson Building, University of Glasgow, Glasgow G12 8QQ, Scotland, UK.
FAU - Vadrevu, Suryakiran
AU  - Vadrevu S
FAU - Dunlop, Allan
AU  - Dunlop A
FAU - Day, Jon
AU  - Day J
FAU - Advant, Noopur
AU  - Advant N
FAU - Troeger, Jessica
AU  - Troeger J
FAU - Klussmann, Enno
AU  - Klussmann E
FAU - Jaffrey, Ellis
AU  - Jaffrey E
FAU - Hay, Ron T
AU  - Hay RT
FAU - Adams, David R
AU  - Adams DR
FAU - Houslay, Miles D
AU  - Houslay MD
FAU - Baillie, George S
AU  - Baillie GS
LA  - eng
GR  - G0600765/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100428
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Protein Isoforms)
RN  - 0 (SUMO-1 Protein)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - COS Cells
MH  - Cells, Cultured
MH  - Chlorocebus aethiops
MH  - Cyclic AMP-Dependent Protein Kinases/*metabolism
MH  - Cyclic Nucleotide Phosphodiesterases, Type 4/genetics/*metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Humans
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Protein Conformation
MH  - Protein Isoforms/genetics/metabolism
MH  - SUMO-1 Protein/*metabolism
MH  - Signal Transduction
EDAT- 2010/03/04 06:00
MHDA- 2010/06/15 06:00
CRDT- 2010/03/04 06:00
PHST- 2010/03/04 06:00 [entrez]
PHST- 2010/03/04 06:00 [pubmed]
PHST- 2010/06/15 06:00 [medline]
AID - BJ20091672 [pii]
AID - 10.1042/BJ20091672 [doi]
PST - epublish
SO  - Biochem J. 2010 Apr 28;428(1):55-65. doi: 10.1042/BJ20091672.