Altered pharmacology of chemokine receptors CXCR1 and CXCR2 hetero-oligomers

Life Sciences 2007 (2007) Proc Life Sciences, PC446

Poster Communications: Altered pharmacology of chemokine receptors CXCR1 and CXCR2 hetero-oligomers

S. Appelbe1, G. Milligan1

1. Biochemistry and Molecular Biology, University of Glasgow, Glasgow, United Kingdom.

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CXCR1 and CXCR2 are members of the chemokine receptor family. The receptors are highly homologous and share 78% sequence identity. CXCL8 (IL-8) is an agonist at both CXCR1 and CXCR2 while CXCR2 can bind several other chemokines including CXCL1 (GRO-α). CXCR1 and CXCR2 have been implicated in a number of inflammatory disease states and are of great interest as potential drug targets. Previous studies have determined that CXCR1 and CXCR2 form homo- and hetero-oligomers with equal apparent affinities (Wilson et al.,2005). In order to investigate the functionality of the CXCR1 and CXCR2 homo- and hetero-oligomers, stable cell lines were generated in which the receptors could be both singly and co-expressed. Using these cell lines we observed; (1) when individually expressed CXCR1 and CXCR2 both undergo prominent CXCL8 induced internalisation. (2) Upon stable co-expression of CXCR1 and CXCR2, the internalisation of CXCR1 in response to CXCL8 is significantly inhibited while CXCR2 undergoes prominent CXCL8 mediated internalisation. (3) Exposure to CXCL1 causes a rapid and transient increase in cell surface CXCR1 expression whilst CXCR2 undergoes rapid internalisation.



Where applicable, experiments conform with Society ethical requirements.

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