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

doi:10.1083/jcb.144.4.755

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J. Cell Biol., Volume 144, Number 4, February 22, 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 mediatetheir effects via interaction with seven transmembrane G protein-coupledreceptors (GPCR). Using CCR5-transfected HEK-293 cells, we showthat both the CCR5 ligand, RANTES, as well as its derivative,aminooxypentane (AOP)- RANTES, trigger immediate responses suchas Ca²⁺ influx, receptor dimerization, tyrosine phosphorylation, andG $alpha$ _i as well as JAK/STAT association to the receptor. In contrastto RANTES, (AOP)-RANTES is unable to trigger late responses, asmeasured by the association of focal adhesion kinase (FAK) tothe chemokine receptor complex, impaired cell polarization requiredfor migration, or chemotaxis. The results are discussed in thecontext of the dissociation of the late signals, provoked by thechemokines required for cell migration, from earlysignals.

Key words: chemokines; receptor dimerization; inflammation; HIV-1

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