Neumann-Giesen Carolin, Fernow Inga, Amaddii Monia, Tikkanen Ritva
Institute of Biochemistry II, University Clinic of Frankfurt am Main and Cluster of Excellence, Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
J Cell Sci. 2007 Feb 1;120(Pt 3):395-406. doi: 10.1242/jcs.03336. Epub 2007 Jan 9.
Cholesterol and sphingolipid-rich membrane microdomains or rafts have been shown to be involved in signaling through many growth factor receptors but the molecular details of these processes are not well understood. The reggie/flotillin proteins are ubiquitously expressed proteins with a poorly characterized function. They are constitutively associated with membrane rafts by means of acylation and oligomerization. Previous studies have implicated reggies in signaling, regulation of actin cytoskeleton and in membrane transport processes. In this study, we analyzed the putative role of reggie-1/flotillin-2 in signaling through the epidermal growth factor receptor. We show that reggie-1 becomes phosphorylated by Src kinase at several tyrosines upon stimulation of cells with epidermal growth factor. In addition, Src and reggie-1 are present as a molecular complex. Epidermal growth factor stimulation of cells results in a Tyr163-dependent translocation of reggie-1 from the plasma membrane into endosomes. We also show that reggie-1 is capable of enhancing the spreading of cells, again in a tyrosine-dependent manner, and knockdown of reggie-1 interferes with spreading. Thus, we reveal a new function for reggie-1 in the regulation of cell adhesion and actin dynamics and in growth factor signaling.
富含胆固醇和鞘脂的膜微区或脂筏已被证明参与通过多种生长因子受体的信号传导，但这些过程的分子细节尚未完全了解。瑞吉蛋白/弗洛蒂林蛋白是普遍表达的蛋白质，其功能特征不明确。它们通过酰化和寡聚化与膜脂筏组成性结合。先前的研究表明瑞吉蛋白参与信号传导、肌动蛋白细胞骨架的调节以及膜运输过程。在本研究中，我们分析了瑞吉蛋白-1/弗洛蒂林-2在通过表皮生长因子受体的信号传导中的假定作用。我们发现，在用表皮生长因子刺激细胞后，瑞吉蛋白-1在几个酪氨酸位点被Src激酶磷酸化。此外，Src和瑞吉蛋白-1以分子复合物的形式存在。表皮生长因子刺激细胞导致瑞吉蛋白-1以Tyr163依赖的方式从质膜转运到内体。我们还表明，瑞吉蛋白-1能够再次以酪氨酸依赖的方式增强细胞的铺展，并且敲低瑞吉蛋白-1会干扰铺展。因此，我们揭示了瑞吉蛋白-1在调节细胞黏附、肌动蛋白动力学和生长因子信号传导中的新功能。
