TABLE 2

Reported in vivo roles of arrestin-dependent signaling

Physiologic Process	Receptor	Arrestin	Proposed/Possible Effector Pathway(s)	References
Embryologic development
Hedgehog signaling
Hematopoiesis	Smoothened^{^a}	z-Arr2	YY1 transcription factor	Yu et al., 2008
Embryo patterning	Smoothened^{^a}	z-Arr3	Gli family transcription factors	Wilbanks et al., 2004
Retinal function
Autosomal dominant retinitis pigmentosa	Rhodopsin K296E	Arr1	N.D.	Li et al., 1995
Photoreceptor cell apoptosis	Rhodopsin	d-Arr1	RdgC-inhibition of caspase-dependent cell death	Alloway et al., 2000; Kiselev et al., 2000
Dopamine-dependent behaviors
Attenuation of dopamine-dependent hyperactivity	Dopamine D2	Arr3	Activation of GSK3β by arrestin3-PP2A-Akt complex	Beaulieu et al., 2004, 2005
Lithium and neuroleptic drug action	Dopamine D2	Arr3	Blockade of arrestin-dependent GSK3β activation	Beaulieu et al., 2008; Masri et al., 2008
Cardiovascular regulation
Cardiomyocyte hypertrophy; bradycardia	Angiotensin AT1a	N.D.	Src; ERK1/2; p90RSK	Zhai et al., 2005
Aldosterone secretion and volume retention	Angiotensin AT1a	Arr2	ERK1/2; upregulated StAR expression	Lymperopoulos et al., 2009
Cardiomyocyte survival in heart failure	β1 adrenergic	Arr3	Src-dependent EGF receptor transactivation	Noma et al., 2007
Vascular smooth muscle neointimal hyperplasia	N.D.	Arr3	ERK1/2; EGF receptor transactivation; p90RSK-Akt	Ahn et al., 2009; Kim et al., 2008
Cutaneous vasodilation and flushing	GPR109A	Arr2	cPLA2-prostaglandin D2 pathway activation	Walters et al., 2009
Skeletal remodelling
Stimulation of osteoblastic bone formation	PTH1	Arr3	N.D.	Gesty-Palmer et al., 2009
Immune system function
Allergen-induced Th2 lymphocyte chemotaxis	N.D.	Arr3	N.D.	Walker et al., 2003
Inhibition of neutrophil chemotaxis	CXCR2	Arr3	N.D.	Su et al., 2005
Inhibition of chemotaxis and cytokine production	TLR4^{^a}	Arr3	ERK1/2 activation; IκB-NFκB inhibition	Basher et al., 2008
Inhibition of NK cell cytotoxicity	KIR2DL1^{^a}	Arr3	SHP-1, SHP-2 dependent signaling	Yu et al., 2008
Tumor growth and metastasis
Bladder cancer proliferation; migration; metastasis	Thromboxane TP-β	Arr3	ERK1/2; FAK	Moussa et al., 2008
Breast cancer invasion; metastasis	LPA1; LPA2	Arr2	Ral, Ral-GDS mediated cytoskeletal rearrangement	Li et al., 2009
Ovarian cancer progression; metastasis	Endothelin ET-A	Arr2	Src-EGF receptor-ERK1/2-Akt; GSK3β−β-catenin	Rosanò et al., 2009
Phorbol ester-induced papilloma formation	Prostaglandin EP2	Arr2	Src-EGF receptor-Ras-ERK1/2-Akt	Chun et al., 2009
Inhibition of tumor cell migration	TGFβ receptor III^{^a}	Arr3	Activation of cdc42; Inhibition of NFκB	Mythreye and Blobe, 2009; You et al., 2009
Androgen-independent prostate cancer growth	Androgen receptor^{^a}	Arr3	Mdm2-dependent AR ubiquitination/degradation	Lakshmikanthan et al., 2009
Metabolic regulation
Increased insulin sensitivity	Insulin receptor^{^a}	Arr3	IR-Akt-Src complex assembly	Luan et al., 2009

z-, Zebrafish arrestin; d-, D. melanogaster arrestin; N.D., not determined.
↵a Non-GPCR.