Regulation of mitogenic signalling via the Gab2 docking protein

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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.