TABLE 2

The nonreceptor arrestin interactome

EffectorArrestinReported FunctionReferences
Clathrin heavy chain
β2-adaptin subunit of AP-2β-Arrestin1Clathrin-dependent GPCR endocytosisGoodman et al., 1996
β-Arrestin2Krupnick et al., 1997
Laporte et al., 1999
Laporte et al., 2000
Tubulin; microtubulesArrestin1Sequestration of arrestinHanson et al., 2006b
β-Arrestin1Attenuation of MAPK activityHanson et al., 2007a
β-Arrestin2Enhanced ubiquitination of cytoskeletal proteins
Arrestin4
Ca2+-calmodulinArrestin1Cytosolic sequestration of Ca2+-calmodulinWu et al., 2006
β-Arrestin1
β-Arrestin2
Arrestin4
Inositol hexakisphosphateArrestin1Arrestin oligomerizationPalczewski et al., 1991a
β-Arrestin1Rhodopsin bindingGaidarov et al., 1999
β-arrestin2Receptor endocytosisMilano et al., 2006
Arrestin4Arrestin nuclear translocationHanson et al., 2008
Src family tyrosine kinases
c-Src; c-Yes; c-Hck; c-Fgr; c-FynArrestin1ERK1/2 activationLuttrell et al., 1999; DeFea et al., 2000a
β-Arrestin1Dynamin 1 phosphorylationMiller et al., 2000
β-Arrestin2Exocytosis/Granule releaseBarlic et al., 2000; Imamura et al., 2001
Phosphorylation/Destabilization of GRK2Penela et al., 2001
FAK phosphorylationGalet and Ascoli, 2008
EGF receptor transactivationNoma et al., 2007
Phosphorylation of β2 adaptin subunit of AP-2Fessart et al., 2007; Zimmerman et al., 2009
c-Raf1-MEK1/2-ERK1/2β-Arrestin1Activation of cytosolic ERK1/2DeFea et al., 2000b; Luttrell et al., 2001
β-Arrestin2Receptor internalization and traffickingLin et al., 1999; Khoury et al., 2014
p90RSK phosphorylationSeta et al., 2002
Actin cytoskeletal reorganization/chemotaxisGe et al., 2003
ERK1/2-dependent transcriptionGesty-Palmer et al., 2005
Mnk1/eIF4E phosphorylation/protein translationDeWire et al., 2008
ASK1-MKK4-JNK3β-Arrestin2Activation of cytosolic JNK3McDonald et al., 2000; Song et al., 2006
Sequestration of JNK outside the nucleusBreitman et al., 2012
ASK1-MKK3/7-p38 MAPKβ-Arrestin1Scaffolding/Activation of p38 MAPKSun et al., 2002; Yang et al., 2012
β-Arrestin2Inhibition of p38 MAPKZhao et al., 2004
IκBα–IκB kinase α/ββ-Arrestin1Attenuation of NFκB signalingGao et al., 2004; Witherow et al., 2004
β-Arrestin2
Casein kinase IIβ-Arrestin2Activation of CK2Kendall et al., 2011
cAMP phosphodiesterases PDE4D3; PDE4D5β-Arrestin1Attenuation of cAMP signalingPerry et al., 2002; Baillie et al., 2007
β-Arrestin2
Diacylglycerol kinasesβ-Arrestin1Attenuation of PKC signalingNelson et al., 2007
β-Arrestin2
PI 4-phosphate 5-kinase Iαβ-Arrestin1Control of clathrin-dependent GPCR internalizationNelson et al., 2008
β-Arrestin2
Phosphatidylinositol 3-kinaseβ-Arrestin1Localized inhibition of PI3KWang and Defea, 2006
PTENβ-Arrestin1Inhibition of AKT signaling and cell proliferationLima-Fernandes et al., 2011
β-Arrestin2Increased cell migration
PP2A-Akt-GSK3ββ-Arrestin2Inactivation of Akt/GSK3βBeaulieu et al., 2005
Activation of β-catenin signalingBeaulieu et al., 2008
Activation of AktKendall et al., 2011
Phospholipase A2β-Arrestin1Vasodilation and cutaneous flushingWalters et al., 2009
Nitric oxide synthasesβ-Arrestin1Suppression of stress-induced iNOS transcriptionTan et al., 2015
β-Arrestin2Post-translational activation of iNOSKuhr et al., 2010
eNOS-dependent S-nitrosylation of β-arrestin2Ozawa et al., 2008
Cofilin; chronophin; LIM kinaseβ-Arrestin2Actin cytoskeletal reorganization/chemotaxisZoudilova et al., 2007, 2010
Filamin Aβ-Arrestin1Membrane rufflingScott et al., 2006
β-Arrestin2
SHP-1; SHP-2β-Arrestin2Inhibition of NK cell cytotoxicityYu et al., 2008
E3 ubiquitin ligases Mdm2; parkin; Nedd4; AIP4; TRAF6Arrestin1Ubiquitination of β-arrestin2Shenoy et al., 2001
β-Arrestin1Stabilization of GPCR–arrestin complexShenoy and Lefkowitz, 2003
β-Arrestin2Increased p53-mediated apoptosisWang et al., 2003
Inhibition of Toll-like receptor signalingWang et al., 2006
Stabilization of GPCR–arrestin–ERK1/2 signalsomeShenoy et al., 2007
GPCR ubiquitination and downregulationBhandari et al., 2007; Shenoy, et al., 2008
Ubiquitin-specific protease 33β-Arrestin2Deubiquitination of β-arrestin2Shenoy et al., 2009
Control of GPCR internalization
Na+/H+ exchanger1β-Arrestin1Ubiquitination of NHE1 by Nedd4Simonin and Fuster, 2010
Negative regulation of NHE1 activity
Ral-GDSβ-Arrestin1Cytoskeletal reorganization/granule exocytosisBhattacharya et al., 2002
β-Arrestin2
ARF-GAP21β-Arrestin1RhoA activation
Membrane ruffling
ARF6-ARNOβ-Arrestin1GPCR endocytosisClaing et al., 2001; Houndolo et al., 2005
β-Arrestin2
N-ethylmaleimide–sensitive factorβ-Arrestin1Control of GPCR internalizationMcDonald et al., 1999
Dishevelled 2β-Arrestin1Frizzled endocytosis and Wnt signalingChen et al., 2004
Kif3A kinesin motor proteinβ-Arrestin1Targeting and internalization of SmoothenedChen et al., 2004
β-Arrestin2Gli-dependent transcriptionKovacs et al., 2008
Histone acetyltransferase p300β-Arrestin1Transcription of p27 and c-FosKang et al., 2005
Enchancer of zeste homolog 2β-Arrestin1Promote histone H4 acetylation of BCR/ABLQin et al., 2014
Stimulate chronic myelogenous leukemia progression
YY1 transcription factorβ-Arrestin1Repression of cdx4-hox transcriptionYue et al., 2009
PPARγβ-Arrestin1Repression of PPARγ–RXRα transcriptionZhuang et al., 2011
STAT1-TC45β-Arrestin1Dephosphorylation/Inactivation of STAT1Mo et al., 2008
  • BCR, B cell receptor; FAK, focal adhesion kinase; eNOS, endothelial nitric oxide synthase.