Anderie Ines, Schulz Irene, Schmid Andreas
Department of Physiology, University of the Saarland, D-66421, Homburg/Saar, Germany.
Cell Signal. 2007 Mar;19(3):582-92. doi: 10.1016/j.cellsig.2006.08.007. Epub 2006 Aug 25.
The ubiquitously expressed protein tyrosine phosphatase PTP1B is involved in the regulation of numerous cellular signaling pathways. PTP1B is anchored to the ER membrane while many of its substrates are localized to the plasma membrane. This spatial separation raises the question how PTP1B can interact with its targets. In our study we demonstrate direct interaction of PTP1B with the Ser/Thr kinase PKCdelta, the non-receptor tyrosine kinase Src and the insulin receptor which all are key enzymes in cellular signaling cascades. Protein complex formation was visualized in vivo using Bimolecular Fluorescence Complementation (BiFC). We demonstrate that complex formation of PTP1B with plasma membrane-anchored proteins is possible without detachment of PTP1B from the ER. Our data indicate that the dynamic ER membrane network is in constant contact to the plasma membrane. Local attachments of the two membrane systems enable a direct communication of ER- and plasma membrane-anchored proteins. The reported formation of membrane junctions is an important step towards the understanding of signal transmissions between the ER and the plasma membrane.
普遍表达的蛋白酪氨酸磷酸酶PTP1B参与众多细胞信号通路的调控。PTP1B锚定在内质网（ER）膜上，而其许多底物定位于质膜。这种空间上的分隔引发了一个问题，即PTP1B如何与其靶标相互作用。在我们的研究中，我们证明了PTP1B与丝氨酸/苏氨酸激酶PKCδ、非受体酪氨酸激酶Src以及胰岛素受体直接相互作用，这些都是细胞信号级联反应中的关键酶。使用双分子荧光互补（BiFC）在体内观察到了蛋白质复合物的形成。我们证明，PTP1B与质膜锚定蛋白形成复合物是可能的，而无需PTP1B从内质网脱离。我们的数据表明，动态的内质网膜网络与质膜持续接触。这两个膜系统的局部附着使得内质网和质膜锚定蛋白能够直接通信。所报道的膜连接的形成是朝着理解内质网与质膜之间信号传递迈出的重要一步。
