The CXCR1 and CXCR2 receptors form constitutive homo- and heterodimers selectively and with equal apparent affinities.
Both homo- and heterodimeric interactions between the CXCR1 and CXCR2 chemokine receptors were observed following co-expression of forms of these receptors in HEK293 cells using assays, including co-immunoprecipitation, single cell imaging of fluorescence resonance energy transfer, cell surface time-resolved fluorescence resonance energy transfer, and bioluminescence resonance energy transfer. These interactions were constitutive and unaffected by the presence of the agonist interleukin 8 and selective as no significant interactions were noted between either the CXCR1 or CXCR2 receptor and the alpha(1A)-adrenoreceptor. Saturation bioluminescence resonance energy transfer indicated that heteromeric interactions between CXCR1 and CXCR2 were of similar affinity as the corresponding homomeric interactions. A novel endoplasmic reticulum trapping strategy demonstrated that these interactions were initiated during protein synthesis and maturation and prior to cell surface delivery. These studies indicated that CXCR1-CXCR2 heterodimers are as likely to form in cells co-expressing these two chemokine receptors as the corresponding homodimers and stand in contrast to previous studies indicating an inability of the CXCR1 receptor to homodimerize or to interact with the CXCR2 receptor (Trettel, F., Di Bartolomeo, S., Lauro, C., Catalano, M., Ciotti, M. T., and Limatola, C. (2003) J. Biol. Chem. 278, 40980-40988).
Wilson
Shirley
S
Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, United Kingdom.
Wilkinson
Graeme
G
Milligan
Graeme
G
D001483:Base Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D017931:DNA Primers; D019281:Dimerization; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D021381:Protein Transport / Q000187:drug effects; D011869:Radioligand Assay; D023062:Receptors, Interleukin-8A / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
D017931:DNA Primers; D016209:Interleukin-8; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins