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

被引:104
作者
Rimoldi, V
Reversi, A
Taverna, E
Rosa, P
Francolini, M
Cassoni, P
Parenti, M
Chini, B
机构
[1] CNR, Inst Neurosci, Cellular & Mol Pharmacol Sect, I-20129 Milan, Italy
[2] Univ Milan, Dept Pharmacol, I-20122 Milan, Italy
[3] Univ Turin, Dept Biomed Sci & Human Oncol, I-10124 Turin, Italy
[4] Univ Milano Bicocca, Dept Expt & Environm Med & Med Biotechnol, Monza, Italy
关键词
caveolin; oxytocin receptor; MAPK; EGFR; p21;
D O I
10.1038/sj.onc.1206612
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 p21(WAF1/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.
引用
收藏
页码:6054 / 6060
页数:7
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