Data di Pubblicazione:
2022
Citazione:
Phosphoproteomic mapping of CCR5 and ACKR2 signaling properties / A. Vacchini, E. Maffioli, D. Di Silvestre, C. Cancellieri, S. Milanesi, S. Nonnis, S. Badanai, P. Mauri, A. Negri, M. Locati, G. Tedeschi, E.M. Borroni. - In: FRONTIERS IN MOLECULAR BIOSCIENCES. - ISSN 2296-889X. - 9:(2022 Nov 22), pp. 1060555.1-1060555.13. [10.3389/fmolb.2022.1060555]
Abstract:
ACKR2 is an atypical chemokine receptor which is structurally uncoupled from
G proteins and is unable to activate signaling pathways used by conventional
chemokine receptors to promote cell migration. Nonetheless, ACKR2 regulates
inflammatory and immune responses by shaping chemokine gradients in tissues
via scavenging inflammatory chemokines. To investigate the signaling pathways
downstream to ACKR2, a quantitative SILAC-based phosphoproteomic analysis
coupled with a systems biology approach with network analysis, was carried out
on a HEK293 cell model expressing either ACKR2 or its conventional
counterpart CCR5. The model was stimulated with the common agonist
CCL3L1 for short (3 min) and long (30 min) durations. As expected, many of
the identified proteins are known to participate in conventional signal
transduction pathways and in the regulation of cytoskeleton dynamics.
However, our analyses revealed unique phosphorylation and network
signatures, suggesting roles for ACKR2 other than its scavenger activity. In
conclusion, the mapping of phosphorylation events at a holistic level indicated
that conventional and atypical chemokine receptors differ in signaling
properties. This provides an unprecedented level of detail in chemokine
receptor signaling and identifying potential targets for the regulation of
ACKR2 and CCR5 function.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
ACKR2; CCR5; signaling; SILAC; phosphoproteome
Elenco autori:
A. Vacchini, E. Maffioli, D. Di Silvestre, C. Cancellieri, S. Milanesi, S. Nonnis, S. Badanai, P. Mauri, A. Negri, M. Locati, G. Tedeschi, E.M. Borroni
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