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© The Rockefeller University Press, 0021-9525/1999//755 $5.00
The Journal of Cell Biology, Volume 144, Number 4, , 1999 755-765

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

José M. Rodríguez-Frade^*, Antonio J. Vila-Coro^*, Ana Martín^*, Marta Nieto, Francisco Sánchez-Madrid, Amanda E.I. Proudfoot, Timothy N.C. Wells, Carlos Martínez-A^*, and Mario Mellado^*

^* Department of Immunology and Oncology, Centro Nacional de Biotecnología, CSIC/UAM, Campus de Cantoblanco, E-28049 Madrid, Spain; Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Diego de León 62, E-28006 Madrid, Spain; and Serono Pharmaceutical Research Institute, Plan-les-Ouates, Geneva CH-1228, Switzerland

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 G_i 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.

Key Words: chemokines • receptor dimerization • inflammation • HIV-1

Abbreviations used in this paper: DSS, disuccinimidyl suberate; FAK, focal adhesion kinase; FN, fibronectin; GPCR, G protein–coupled receptors; JAK, Janus associated kinase; PTX, pertussis toxin.

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