Oxytocin receptor elicits different EGFR/MAPK activation patterns depending on its localization in caveolin-1 enriched domains

Valeria Rimoldi, Alessandra Reversi, Elena Taverna, Patrizia Rosa, Maura Francolini, Paola Cassoni, Marco Parenti, Bice Chini

Research output: Contribution to journalArticlepeer-review

Abstract

We have recently shown that oxytocin inhibits cell proliferation when the vast majority of oxytocin receptors are excluded from caveolin-1-enriched microdomains, and that, on the contrary, it has a mitogenic effect when the receptors are targeted to these plasma membrane domains. In this study, we investigated whether the receptors located inside and outside caveolar microdomains initiate different signalling pathways and how this may lead to opposite effects on cell proliferation. Our data indicate that, depending on their localization, oxytocin receptors transactivate EGFR and activate ERK1/2 using different signalling intermediates. The final outcome is a different temporal pattern of EGFR and ERK1/2 phosphorylation, which is more persistent when the receptors are located outside caveolar microdomains and inhibit cell growth, and very transient when they are located in caveolar microdomains and stimulate cell growth. Finally, only the activation of receptors located outside caveolar microdomains correlates with the activation of the cell cycle inhibitor p21WAF1/CIP1, thus suggesting that the antiproliferative OTR effects may, in this case, be achieved by a sustained activation of EGFR and MAPK leading to the induction of this cell cycle regulator.

Original languageEnglish
Pages (from-to)6054-6060
Number of pages7
JournalOncogene
Volume22
Issue number38
DOIs
Publication statusPublished - Sep 4 2003

Keywords

  • Caveolin
  • EGFR
  • MAPK
  • Oxytocin receptor
  • p21

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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