Insulin‐like growth factor binding protein‐3 increases intracellular calcium concentrations in MCF‐7 breast carcinoma cells

FEBS Letters

Binoux, Michel¹  Ricort, Jean-Marc¹  Lombet, Alain²  Lassarre, Claudine¹ 

[1] Institut National de la Santé et de la Recherche Médicale, Unité 515, Hôpital Saint-Antoine, 184 rue du Fbg St-Antoine, 75012 Paris, France;INSERM U 339, Hôpital Saint-Antoine, 184 rue du Fbg St-Antoine, 75012 Paris, France

关键词: Insulin-like growth factor binding protein-3;    Intracellular calcium;    Breast carcinoma cell;    Gi protein-coupled receptor;   

DOI  :  10.1016/S0014-5793(02)03250-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Insulin-like growth factor binding protein-3, IGFBP-3, specifically binds to IGFs with high affinity, but it is also capable of modulating the IGF-I signalling pathway or inducing apoptosis independently of its binding to IGFs. The molecular mechanisms underlying the action of IGFBP-3 have not been elucidated. In this study, we have demonstrated that binding of IGFBP-3 to a cell surface receptor in MCF-7 breast carcinoma cells induces a rapid and transient increase in intracellular free calcium. This increase was mediated via a pertussis toxin-sensitive pathway, indicating that the IGFBP-3 receptor may be specifically coupled to a Gi protein. The effect of IGFBP-3 on calcium concentrations was dose-dependent and also occurred when IGFBP-3 was complexed with either IGF-I or heparin, suggesting that the receptor binding site is probably located in the least conserved central domain of IGFBP-3. Neither IGFBP-1, nor IGFBP-5 (structurally the closest to IGFBP-3) altered intracellular calcium concentrations. These results provide evidence that a specific intracellular signal is triggered by IGFBP-3 binding to a cell surface receptor.

【 授权许可】

Unknown