Journal
EMBO JOURNAL
Volume 20, Issue 10, Pages 2497-2507Publisher
WILEY
DOI: 10.1093/emboj/20.10.2497
Keywords
chemokine receptor; dimerization; G proteins; phosphatidyl inositol 3-kinase
Categories
Ask authors/readers for more resources
Chemokine receptors of both the CC and CXC families have been demonstrated to undergo a ligand-mediated homodimerization process required for Ca2+ flux and chemotaxis. We show that, in the chemokine response, heterodimerization is also permitted between given receptor pairs, specifically between CCR2 and CCR5, This has functional consequences, as the CCR2 and CCR5 ligands monocyte chemotactic protein-1 (MCP-1) and RANTES (regulated upon activation, normal T cen-expressed and Secreted) cooperate to trigger calcium responses at concentrations 10- to 100-fold lower than the threshold for either chemokine alone. Heterodimerization results in recruitment of each receptor-associated signaling complex, but also recruits dissimilar signaling pathways such as G(q/11) association, and delays activation of phosphatidyl inositol 3-kinase, The consequences are a pertussis toxin-resistant Ca2+ flux and triggering of cell adhesion rather than chemotaxis, These results show the effect of heterodimer formation on increasing the sensitivity and dynamic range of the chemokine response, and may aid in understanding the dynamics of leukocytes at limiting chemokine concentrations in vivo.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available