Similarities and differences in RANTES- and (AOP)-RANTES-triggered signals: implications for chemotaxis.
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.
Department of Immunology and Oncology, Centro Nacional de Biotecnolog¿ia, CSIC/UAM, Campus de Cantoblanco, E-28049 Madrid, Spain.
J M
JM
Rodríguez-Frade
A J
AJ
Vila-Coro
A
A
Martín
M
M
Nieto
F
F
Sánchez-Madrid
A E
AE
Proudfoot
T N
TN
Wells
C
C
Martínez-A
M
M
Mellado
D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D018946:Chemokine CCL5 / Q000031:analogs & derivatives* / Q000502:physiology*; D002633:Chemotaxis / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D053613:Janus Kinase 1; D008894:Milk Proteins; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019713:Receptors, CCR5 / Q000235:genetics / Q000502:physiology; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
D015815:Cell Adhesion Molecules; D018946:Chemokine CCL5; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D019713:Receptors, CCR5; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; C111989:aminooxypentane-RANTES; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1; C496050:PTK2 protein, human; D019204:GTP-Binding Proteins