Distinct motifs in the chemokine receptor CCR7 regulate signal transduction, receptor trafficking and chemotaxis

Carolina Otero, Petra S. Eisele, Karin Schaeuble, Marcus Groettrup, Daniel F. Legler

Resultado de la investigación: Article

32 Citas (Scopus)

Resumen

The chemokine receptor CCR7, together with its ligands CCL19 and CCL21, is responsible for the correct homing and trafficking of dendritic cells and lymphocytes to secondary lymphoid tissues. Moreover, cancer cells can utilize CCR7 to metastasize to draining lymph nodes. However, information on CCR7 signaling leading to cell migration or receptor trafficking is sparse. Using novel CCR7 deletion mutants with successive truncations of the intracellular C-terminus and a mutant with impaired G-protein coupling, we identified distinct motifs responsible for various aspects of CCR7 signal transduction. Deleting a Ser/Thr motif at the tip of the intracellular tail of CCR7 resulted in an impaired chemokine-mediated activation of Erk1/2 kinases. Interestingly, deleting an additional adjacent motif restored the ability of CCL19-mediated Erk1/ 2 phosphorylation, suggesting the presence of a regulatory motif. Both the Ser/Thr and the regulatory motif are dispensable for signaling events leading to cell migration, and receptor trafficking. A CCR7 mutant lacking virtually the complete C-terminus readily bound CCL19 and was internalized, but was unable to activate the G protein and to transmit signals required for cell migration, mobilization of [Ca 2+] i and Erk1/2 activation. Finally, G-protein coupling was critical for [Ca 2+] i mobilization, Erk1/2 phosphorylation and chemotaxis, but not for CCR7 trafficking.

Idioma originalEnglish
Páginas (desde-hasta)2759-2767
Número de páginas9
PublicaciónJournal of Cell Science
Volumen121
N.º16
DOI
EstadoPublished - 15 ago 2008

Huella dactilar

Chemokine Receptors
Chemotaxis
GTP-Binding Proteins
Cell Movement
Signal Transduction
Phosphorylation
Aptitude
Lymphoid Tissue
Chemokines
Dendritic Cells
Phosphotransferases
Lymph Nodes
Lymphocytes
Ligands
Neoplasms

ASJC Scopus subject areas

  • Cell Biology

Citar esto

Otero, Carolina ; Eisele, Petra S. ; Schaeuble, Karin ; Groettrup, Marcus ; Legler, Daniel F. / Distinct motifs in the chemokine receptor CCR7 regulate signal transduction, receptor trafficking and chemotaxis. En: Journal of Cell Science. 2008 ; Vol. 121, N.º 16. pp. 2759-2767.
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abstract = "The chemokine receptor CCR7, together with its ligands CCL19 and CCL21, is responsible for the correct homing and trafficking of dendritic cells and lymphocytes to secondary lymphoid tissues. Moreover, cancer cells can utilize CCR7 to metastasize to draining lymph nodes. However, information on CCR7 signaling leading to cell migration or receptor trafficking is sparse. Using novel CCR7 deletion mutants with successive truncations of the intracellular C-terminus and a mutant with impaired G-protein coupling, we identified distinct motifs responsible for various aspects of CCR7 signal transduction. Deleting a Ser/Thr motif at the tip of the intracellular tail of CCR7 resulted in an impaired chemokine-mediated activation of Erk1/2 kinases. Interestingly, deleting an additional adjacent motif restored the ability of CCL19-mediated Erk1/ 2 phosphorylation, suggesting the presence of a regulatory motif. Both the Ser/Thr and the regulatory motif are dispensable for signaling events leading to cell migration, and receptor trafficking. A CCR7 mutant lacking virtually the complete C-terminus readily bound CCL19 and was internalized, but was unable to activate the G protein and to transmit signals required for cell migration, mobilization of [Ca 2+] i and Erk1/2 activation. Finally, G-protein coupling was critical for [Ca 2+] i mobilization, Erk1/2 phosphorylation and chemotaxis, but not for CCR7 trafficking.",
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Distinct motifs in the chemokine receptor CCR7 regulate signal transduction, receptor trafficking and chemotaxis. / Otero, Carolina; Eisele, Petra S.; Schaeuble, Karin; Groettrup, Marcus; Legler, Daniel F.

En: Journal of Cell Science, Vol. 121, N.º 16, 15.08.2008, p. 2759-2767.

Resultado de la investigación: Article

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AU - Eisele, Petra S.

AU - Schaeuble, Karin

AU - Groettrup, Marcus

AU - Legler, Daniel F.

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AB - The chemokine receptor CCR7, together with its ligands CCL19 and CCL21, is responsible for the correct homing and trafficking of dendritic cells and lymphocytes to secondary lymphoid tissues. Moreover, cancer cells can utilize CCR7 to metastasize to draining lymph nodes. However, information on CCR7 signaling leading to cell migration or receptor trafficking is sparse. Using novel CCR7 deletion mutants with successive truncations of the intracellular C-terminus and a mutant with impaired G-protein coupling, we identified distinct motifs responsible for various aspects of CCR7 signal transduction. Deleting a Ser/Thr motif at the tip of the intracellular tail of CCR7 resulted in an impaired chemokine-mediated activation of Erk1/2 kinases. Interestingly, deleting an additional adjacent motif restored the ability of CCL19-mediated Erk1/ 2 phosphorylation, suggesting the presence of a regulatory motif. Both the Ser/Thr and the regulatory motif are dispensable for signaling events leading to cell migration, and receptor trafficking. A CCR7 mutant lacking virtually the complete C-terminus readily bound CCL19 and was internalized, but was unable to activate the G protein and to transmit signals required for cell migration, mobilization of [Ca 2+] i and Erk1/2 activation. Finally, G-protein coupling was critical for [Ca 2+] i mobilization, Erk1/2 phosphorylation and chemotaxis, but not for CCR7 trafficking.

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