Small Molecule Allosteric Modulators of Phosphodiesterase 4 - Phosphodiesterases as Drug Targets - page 176

Table 2 PDE4 accessory proteins and their effect on PDE4 localization, enzymatic activity and sensitivity to inhibition by rolipram
Accessory
protein

Site on PDE4 PDE4

isoforms

Effect Rolipram

sensitivity

References

AIP/XAP2/
ARA9

N-terminus and
UCR2

4A4/5, 4D4 Inhibits PDE4 activity Increased Bolger et al. ( 2003b )

AKAP149 unknown 4A Anchoring to mitochondria Asirvatham et al. ( 2004 )

AKAP18 N-terminus 4D3/9 Anchoring to water channel

aquaporin-2-bearing vesicles

Stefan et al. ( 2007 )

AKAP9 N-terminus 4D3, not 4D5 Anchoring to cardiac I(Ks) potassium channel Terrenoire et al. ( 2009 )

AKAP95 unknown 4A Anchoring to nucleus Asirvatham et al. ( 2004 )

b -arrestin N-terminus and

catalytic domain

4D5, not 4D3 Dynamic recruitment to b 2 -adrenergic receptor,
prevents ERK1 phosphorylation

unknown Bolger et al. ( 2003a , 2006 ),

Baillie et al. ( 2007 )

DISC1 UCR2 Inhibits PDE4 activity unknown Murdoch et al. ( 2007 )

ERK1 Catalytic domain All Inhibits activity of long forms of PDE4 unknown Hoffmann et al. ( 1999 ),

MacKenzie et al. ( 2000 )

Lyn, Fyn, Src N-terminus, LR2

linker

4A4/5, 4D4 Anchoring to SH3-domain kinases Increased McPhee et al. ( 1999 )

mAKAP N-terminus 4D3 Anchoring to cardiomyocyte perinuclear region Carlisle Michel et al. ( 2004 )

MTG unknown 4A AKAP anchoring to golgi Asirvatham et al. ( 2004 )

myomegalin UCR2 Activates PDE4 activity Decreased? Verde et al. ( 2001 )

PKA UCR1 long forms Activates PDE4 activity Sette and Conti ( 1996 ),

Hoffmann et al. ( 1998 )

RACK1 N-terminus, C-

terminal helix

4D5 Anchoring to WD repeat proteins Yarwood et al. ( 1999 ), Bolger

et al. ( 2006 )

RyR2
ryanodine
receptor

N-terminus 4D3, not 4D5 Anchoring Lehnart et al. ( 2005 )