Grant: Project Grant

Cells respond to their environment by special protein signals binding cell surface receptors, which then relay this binding to other proteins inside the cell. Some signals may instruct the cell to start dividing, to move away from the signal, to change into a different kind of a cell or to simply stop doing whatever it is doing. Various disease states may change or subvert such signalling events such that, for example, cancerous cells may become unresponsive to signals that tell them to stop dividing, or tissues that normally remain separated may become aberrantly intermingled. Eph receptors mediate many such signalling events and have been implicated in diseases such as cancer and neurodegeneration, but the precise details of Eph signalling are still unknown. External signal binding to Eph receptors causes them to bind to other proteins inside the cell, and to activate their function, which in turn causes them to bind other proteins and so on, causing the activation of a signalling cascade. Such a chain of events eventually reaches some key cellular compartments like for example the cellular skeleton, which may change its shape and result in cell movement. We propose to study a protein that may participate in such a chain originating from Eph receptors. This protein, called MYCBP2, has been involved in diseases and developmental malformations suggesting that its function is critical for normal cellular signalling in humans.