Modulation of chemokine receptor activity through dimerization and crosstalk |
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Authors: | C L Salanga M O’Hayre T Handel |
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Institution: | (1) Skaggs School of Pharmacy and Pharmaceutical Science, University of California, San Diego, La Jolla, CA 92093-0684, USA |
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Abstract: | Chemokines are small, secreted proteins that bind to the chemokine receptor subfamily of class A G protein-coupled receptors.
Collectively, these receptor-ligand pairs are responsible for diverse physiological responses including immune cell trafficking,
development and mitogenic signaling, both in the context of homeostasis and disease. However, chemokines and their receptors
are not isolated entities, but instead function in complex networks involving homo- and heterodimer formation as well as crosstalk
with other signaling complexes. Here the functional consequences of chemokine receptor activity, from the perspective of both
direct physical associations with other receptors and indirect crosstalk with orthogonal signaling pathways, are reviewed.
Modulation of chemokine receptor activity through these mechanisms has significant implications in physiological and pathological
processes, as well as drug discovery and drug efficacy. The integration of signals downstream of chemokine and other receptors
will be key to understanding how cells fine-tune their response to a variety of stimuli, including therapeutics.
Received 19 October 2008; received after revision 7 November 2008; accepted 11 November 2008
C. L. Salanga, M. O’Hayre: These authors contributed equally. |
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Keywords: | " target="_blank"> Chemokine chemokine receptor dimerization crosstalk synergy signal transduction |
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