TABLE 2

Summary of ACKR3 signaling

Primary	Secondary	Function	Studied System	Reference
G protein–dependent signaling
Primary
Gα_i1	No activation, but a constitutive recruitment		HEK293 cells	Levoye et al., 2009
	No activation		HEK293 cells	Hoffmann et al., 2012
Gα_i/o	ERK/Akt activation		Primary rodent astrocytes	Ödemis et al., 2012
G protein–independent signaling
Primary
β-arrestin-1/2	Akt and MAPK activation		Primary rodent astrocytes	Ödemis et al., 2012
	JAK2/STAT3 pathway		Human bladder cancer cells	Hao et al., 2012
	ERK1/2 phosphorylation		Glioma cells	Hattermann et al., 2010
			HEK293 cells	Rajagopal et al., 2010
	No ERK1/2 phosphorylation		Rat VSMCs	Rajagopal et al., 2010
	Internalization		HEK293 cells	Canals et al., 2012
			HEK293 cells	Ray et al., 2012
			Breast cancer cells	Luker et al., 2010
	Akt phosphorylation		PB CD34+ cells	Torossian et al., 2014
Influence on signaling due to coexpression/oligomerization
Influence on/oligomer with…	Effect	Secondary Effect
ACKR3 (homomer)	Unknown		HEK293 cells	Levoye et al., 2009
			HEK293T cells	Kalatskaya et al., 2009
α₁-AR	Negative regulation of α₁-AR		Human VSMCs	Albee et al., 2017
EGFR	CXCR7 involved in phosphorylation of EGFR		Breast cancer cells	Salazar et al., 2014
	Mitosis of breast cancer cells		Breast cancer cells	Salazar et al., 2014
CXCR4	ACKR3 scavenges CXCL12 from CXCR4	Fine tuning of primordial germ cell migration	Zebrafish	Boldajipour et al., 2008
			Daudi cells, MDCK, HeLa cells, Raji B-cells, HUVECs,	Naumann et al., 2010
			zebrafish, mouse hearts, human umbilical cords
		Creating chemokine gradient for migration	Zebrafish lateral line primordium	Donà et al., 2013
	ACKR3 defines directionality of migration		Zebrafish lateral line primordium	Dambly-Chaudière et al., 2009
	ACKR3 negatively modulates CXCR4-mediated lymphocyte integrin adhesiveness		T lymphocytes, CD34+ cells	Hartmann et al., 2008
	Potentiation of Ca²⁺ flux^a		HEK293 cells	Sierro et al., 2007
	Negative modulation of Ca²⁺ flux^a		HEK293 cells	Levoye et al., 2009
	Delay of ERK phosphorylation		HEK293 cells	Sierro et al., 2007
	Enhancement of p38 MAPK and SAPK pathways		HEK293 cells	Decaillot et al., 2011
	Heteromer constitutively recruits β-arrestin-2^a	Enhanced cell migration^a	HEK293 cells, MDA-MB-231, U87 cells	Decaillot et al., 2011
	Reduced inhibition of cAMP production		HEK293 cells	Decaillot et al., 2011
	Decreased potency for ³⁵GTPγS binding after CXCR4 activation		HEK293 cells	Levoye et al., 2009
	ACKR3 inhibits migration by CXCR4 for low CXCL12 dose^a		T lymphocytes	Levoye et al., 2009

↵^a Controversies between studies.
³⁵GTPγS, guanosine 5′-O-(3-[³⁵S]thio)triphosphate; JAK2, Janus kinase 2; MAPK, mitogen-activated protein kinase; PB, peripheral blood; SAPK, stress-activated protein kinase; STAT3, signal transducer and activator of transcription 3.