TABLE 2.

The nonreceptor arrestin interactome

Effector	Arrestin	Reported Function	References
Clathrin heavy chain β2-adaptin subunit of AP-2	β-Arrestin1	Clathrin-dependent GPCR endocytosis	Goodman et al., 1996
	β-Arrestin2		Krupnick et al., 1997
			Laporte et al., 1999
			Laporte et al., 2000
Tubulin; microtubules	Arrestin1	Sequestration of arrestin	Hanson et al., 2006b
	β-Arrestin1	Attenuation of MAPK activity	Hanson et al., 2007a
	β-Arrestin2	Enhanced ubiquitination of cytoskeletal proteins
	Arrestin4
Ca2+-calmodulin	Arrestin1	Cytosolic sequestration of Ca2+-calmodulin	Wu et al., 2006
	β-Arrestin1
	β-Arrestin2
	Arrestin4
Inositol hexakisphosphate	Arrestin1	Arrestin oligomerization	Palczewski et al., 1991a
	β-Arrestin1	Rhodopsin binding	Gaidarov et al., 1999
	β-arrestin2	Receptor endocytosis	Milano et al., 2006
	Arrestin4	Arrestin nuclear translocation	Hanson et al., 2008
Src family tyrosine kinases c-Src; c-Yes; c-Hck; c-Fgr; c-Fyn	Arrestin1	ERK1/2 activation	Luttrell et al., 1999; DeFea et al., 2000a
	β-Arrestin1	Dynamin 1 phosphorylation	Miller et al., 2000
	β-Arrestin2	Exocytosis/Granule release	Barlic et al., 2000; Imamura et al., 2001
		Phosphorylation/Destabilization of GRK2	Penela et al., 2001
		FAK phosphorylation	Galet and Ascoli, 2008
		EGF receptor transactivation	Noma et al., 2007
		Phosphorylation of β2 adaptin subunit of AP-2	Fessart et al., 2007; Zimmerman et al., 2009
c-Raf1-MEK1/2-ERK1/2	β-Arrestin1	Activation of cytosolic ERK1/2	DeFea et al., 2000b; Luttrell et al., 2001
	β-Arrestin2	Receptor internalization and trafficking	Lin et al., 1999; Khoury et al., 2014
		p90RSK phosphorylation	Seta et al., 2002
		Actin cytoskeletal reorganization/chemotaxis	Ge et al., 2003
		ERK1/2-dependent transcription	Gesty-Palmer et al., 2005
		Mnk1/eIF4E phosphorylation/protein translation	DeWire et al., 2008
ASK1-MKK4-JNK3	β-Arrestin2	Activation of cytosolic JNK3	McDonald et al., 2000; Song et al., 2006
		Sequestration of JNK outside the nucleus	Breitman et al., 2012
ASK1-MKK3/7-p38 MAPK	β-Arrestin1	Scaffolding/Activation of p38 MAPK	Sun et al., 2002; Yang et al., 2012
	β-Arrestin2	Inhibition of p38 MAPK	Zhao et al., 2004
IκBα–IκB kinase α/β	β-Arrestin1	Attenuation of NFκB signaling	Gao et al., 2004; Witherow et al., 2004
	β-Arrestin2
Casein kinase II	β-Arrestin2	Activation of CK2	Kendall et al., 2011
cAMP phosphodiesterases PDE4D3; PDE4D5	β-Arrestin1	Attenuation of cAMP signaling	Perry et al., 2002; Baillie et al., 2007
	β-Arrestin2
Diacylglycerol kinases	β-Arrestin1	Attenuation of PKC signaling	Nelson et al., 2007
	β-Arrestin2
PI 4-phosphate 5-kinase Iα	β-Arrestin1	Control of clathrin-dependent GPCR internalization	Nelson et al., 2008
	β-Arrestin2
Phosphatidylinositol 3-kinase	β-Arrestin1	Localized inhibition of PI3K	Wang and Defea, 2006
PTEN	β-Arrestin1	Inhibition of AKT signaling and cell proliferation	Lima-Fernandes et al., 2011
	β-Arrestin2	Increased cell migration
PP2A-Akt-GSK3β	β-Arrestin2	Inactivation of Akt/GSK3β	Beaulieu et al., 2005
		Activation of β-catenin signaling	Beaulieu et al., 2008
		Activation of Akt	Kendall et al., 2011
Phospholipase A2	β-Arrestin1	Vasodilation and cutaneous flushing	Walters et al., 2009
Nitric oxide synthases	β-Arrestin1	Suppression of stress-induced iNOS transcription	Tan et al., 2015
	β-Arrestin2	Post-translational activation of iNOS	Kuhr et al., 2010
		eNOS-dependent S-nitrosylation of β-arrestin2	Ozawa et al., 2008
Cofilin; chronophin; LIM kinase	β-Arrestin2	Actin cytoskeletal reorganization/chemotaxis	Zoudilova et al., 2007, 2010
Filamin A	β-Arrestin1	Membrane ruffling	Scott et al., 2006
	β-Arrestin2
SHP-1; SHP-2	β-Arrestin2	Inhibition of NK cell cytotoxicity	Yu et al., 2008
E3 ubiquitin ligases Mdm2; parkin; Nedd4; AIP4; TRAF6	Arrestin1	Ubiquitination of β-arrestin2	Shenoy et al., 2001
	β-Arrestin1	Stabilization of GPCR–arrestin complex	Shenoy and Lefkowitz, 2003
	β-Arrestin2	Increased p53-mediated apoptosis	Wang et al., 2003
		Inhibition of Toll-like receptor signaling	Wang et al., 2006
		Stabilization of GPCR–arrestin–ERK1/2 signalsome	Shenoy et al., 2007
		GPCR ubiquitination and downregulation	Bhandari et al., 2007; Shenoy, et al., 2008
Ubiquitin-specific protease 33	β-Arrestin2	Deubiquitination of β-arrestin2	Shenoy et al., 2009
		Control of GPCR internalization
Na+/H+ exchanger1	β-Arrestin1	Ubiquitination of NHE1 by Nedd4	Simonin and Fuster, 2010
		Negative regulation of NHE1 activity
Ral-GDS	β-Arrestin1	Cytoskeletal reorganization/granule exocytosis	Bhattacharya et al., 2002
	β-Arrestin2
ARF-GAP21	β-Arrestin1	RhoA activation
		Membrane ruffling
ARF6-ARNO	β-Arrestin1	GPCR endocytosis	Claing et al., 2001; Houndolo et al., 2005
	β-Arrestin2
N-ethylmaleimide–sensitive factor	β-Arrestin1	Control of GPCR internalization	McDonald et al., 1999
Dishevelled 2	β-Arrestin1	Frizzled endocytosis and Wnt signaling	Chen et al., 2004
Kif3A kinesin motor protein	β-Arrestin1	Targeting and internalization of Smoothened	Chen et al., 2004
	β-Arrestin2	Gli-dependent transcription	Kovacs et al., 2008
Histone acetyltransferase p300	β-Arrestin1	Transcription of p27 and c-Fos	Kang et al., 2005
Enchancer of zeste homolog 2	β-Arrestin1	Promote histone H4 acetylation of BCR/ABL	Qin et al., 2014
		Stimulate chronic myelogenous leukemia progression
YY1 transcription factor	β-Arrestin1	Repression of cdx4-hox transcription	Yue et al., 2009
PPARγ	β-Arrestin1	Repression of PPARγ–RXRα transcription	Zhuang et al., 2011
STAT1-TC45	β-Arrestin1	Dephosphorylation/Inactivation of STAT1	Mo et al., 2008

BCR, B cell receptor; FAK, focal adhesion kinase; eNOS, endothelial nitric oxide synthase.