Regulation of mitogenic signalling via the Gab2 docking protein

细胞增殖受生长因子的调节，生长因子与细胞表面的特定受体结合。然后，这些受体向细胞内部发送信号，指示细胞分裂。在细胞内，信号通过信号蛋白传递。重要的是，生长因子受体或细胞内信号分子的异常信号可能导致癌症。我们最近已经证明，信号蛋白Gab2在乳腺癌的一个子集中过表达。此外，我们还发现了另一种名为PKB的蛋白质，它可以通过Gab2‘关闭’信号传递，而由Gab2失控的信号传递可以使细胞癌变。这个项目的目的是描述PKB是如何调控Gab2的，并调查这一机制在人类癌症中是否受到损害，导致Gab2信号增强。这项研究将提供有关生长因子信号如何在细胞内传递的重要信息，并可能识别新的致癌基因。

Cell proliferation is regulated by growth factors which bind to specific receptors on the cell surface. These receptors then transmit a signal to the interior of the cell instructing it to divide. Inside the cell, the signal is transmitted by signalling proteins. Importantly, aberrant signalling by growth factor receptors or intracellular signalling molecules can contribute to cancer. We have recently demonstrated that the signalling protein Gab2 is overexpressed in a subset of breast cancers. Furthermore, we have identified that another protein, termed PKB, can 'switch off' signalling by Gab2, and that deregulated signalling by Gab2 can make cells cancerous. The aim of this project is to characterize how PKB regulates Gab2, and to investigate whether this mechanism is impaired in human cancers, leading to enhanced Gab2 signalling. The research will provide important information regarding how growth factor signals are transmitted inside cells, and may identify a new cancer-causing gene.