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Rockefeller University Press, Journal of Cell Biology, 4(144), p. 755-765, 1999

DOI: 10.1083/jcb.144.4.755

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Similarities and Differences in RANTES- and (AOP)-RANTES–triggered Signals: Implications for Chemotaxis

Journal article published in 1999 by José M. Rodríguez-Frade, Rodríguez Frade Jm, Antonio J. Vila-Coro, Vila Coro Aj, Ana Martín, Marta Nieto, Francisco Sánchez-Madrid ORCID, Amanda E. I. Proudfoot, Timothy N. C. Wells, Proudfoot Ae, Wells Tn, A. Carlos Martínez, Carlos Martínez-A., Mario Mellado
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Chemokines are a family of proinflammatory cytokines that attract and activate specific types of leukocytes. Chemokines mediate their effects via interaction with seven transmembrane G protein-coupled receptors (GPCR). Using CCR5-transfected HEK-293 cells, we show that both the CCR5 ligand, RANTES, as well as its derivative, aminooxypentane (AOP)- RANTES, trigger immediate responses such as Ca2+ influx, receptor dimerization, tyrosine phosphorylation, and Galphai as well as JAK/STAT association to the receptor. In contrast to RANTES, (AOP)-RANTES is unable to trigger late responses, as measured by the association of focal adhesion kinase (FAK) to the chemokine receptor complex, impaired cell polarization required for migration, or chemotaxis. The results are discussed in the context of the dissociation of the late signals, provoked by the chemokines required for cell migration, from early signals.