Proliferation versus migration in platelet-derived growth factor signaling: The key role of endocytosis

Alina De Donatis, Giusy Comito, Francesca Buricchi, Maria C. Vinci, Astrid Parenti, Anna Caselli, Guido Camici, Giampaolo Manao, Giampietro Ramponi, Paolo Cirri

Research output: Contribution to journalArticle

Abstract

It is common knowledge that platelet-derived growth factor (PDGF) is a critical regulator of mesenchymal cell migration and proliferation. Nevertheless, these two cellular responses are mutually exclusive. To solve this apparent contradiction, we studied the behavior of NIH3T3 fibroblasts in response to increasing concentrations of PDGF. We found that there is strong cell proliferation induction only with PDGF concentrations > 5 ng/ml, whereas the cell migration response arises starting from 1 ng/ml and is negligible at higher PDGF concentrations. According to these phenotypic evidences, our data indicate that cells display a differential activation of the main signaling pathways in response to PDGF as a function of the stimulation dose. At low PDGF concentrations, there is maximal activation of signaling pathways linked to cytoskeleton rearrangement needed for cell motility, whereas high PDGF concentrations activate pathways linked to mitogenesis induction. Our results suggest a mechanism by which cells switch from a migrating to a proliferating phenotype sensing the increasing gradient of PDGF. In addition, we propose that the cell decision to proliferate or migrate relies on different endocytotic routes of the PDGF receptor in response to different PDGF concentrations.

Original languageEnglish
Pages (from-to)19948-19956
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number29
DOIs
Publication statusPublished - Jul 18 2008

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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    De Donatis, A., Comito, G., Buricchi, F., Vinci, M. C., Parenti, A., Caselli, A., Camici, G., Manao, G., Ramponi, G., & Cirri, P. (2008). Proliferation versus migration in platelet-derived growth factor signaling: The key role of endocytosis. Journal of Biological Chemistry, 283(29), 19948-19956. https://doi.org/10.1074/jbc.M709428200