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.

Proliferation vs migration in PDGF signaling: The key role of endocytosis / A.DEDONATIS; G.COMITO; F.BURICCHI; M. VINCI; A.PARENTI; A.CASELLI; G.CAMICI; G.MANAO; G.RAMPONI; P.CIRRI. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - ELETTRONICO. - 283:(2008), pp. 19948-19956. [10.1074/jbc.M709428200]

Proliferation vs migration in PDGF signaling: The key role of endocytosis

VINCI, MARIA CRISTINA;PARENTI, ASTRID;CASELLI, ANNA;CAMICI, GUIDO;MANAO, GIAMPAOLO;RAMPONI, GIAMPIETRO;CIRRI, PAOLO
2008

Abstract

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.
2008
283
19948
19956
A.DEDONATIS; G.COMITO; F.BURICCHI; M. VINCI; A.PARENTI; A.CASELLI; G.CAMICI; G.MANAO; G.RAMPONI; P.CIRRI
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/315499
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