Mechanisms of DLK regulation and action in cell proliferation/Mécanismes de régulation et d'action de la kinase DLK au cours de la proliferation cellulaire

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Cells in multicellular organisms communicate with each other through a number of signaling molecules in order to control their growth, differentiation and metabolism. Information encoded by these molecules is received at the cell surface and transmitted within the cell by networks of signaling pathways that consequently modulate gene expression. Among the key pathways involved in cell proliferation control are those which activate the so-called mitogen-activated protein kinase (MAPK) family of kinases. In human, alterations in regulation and function of MAPKs are associated with various diseases, including diabetes and cancer. As a mean to characterize the molecular mechanisms by which MAPK signaling is regulated in normal cells, our research group investigates the roles and the specific properties of DLK, a MAPK upstream activator that is required for organism development, cell differentiation and cell death. Interestingly, recent experiments carried out in our laboratory have also revealed the involvement of DLK in the response of cells to growth factors. However, exactly how DLK mediates proliferation signals is an important question still not fully answered. Consequently, the overall goal of the present proposal is to clarify further the mechanisms underlying regulation and role of DLK in cell proliferation. This information may have fundamental implications in the design of novel strategies for cancer treatment.