Role of the MAPK kinase kinase DLK in the skin/Rôle de la MAPK kinase kinase DLK dans la peau

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The goal of our research program is to understand the role of protein kinases in the control of cell growth, cell differentiation and cell death. This is of particular interest since alterations in the function of protein kinases can lead to a spectrum of defects ranging from developmental abnormalities to numerous diseases, including cancer. A comprehensive knowledge of protein kinases may help us find new ways to control these disorders. With support from NSERC, we investigate the role and specific properties of dual leucine zipper-bearing kinase (DLK), a serine/threonine kinase that acts as an upstream activator of the stress-responsive c-Jun N-terminal kinases. Through use of molecular and cellular biology approaches, our laboratory has recently accumulated evidence in support of a role for DLK in regulating terminal differentiation of keratinocytes, the major cell type of the epidermis. Whether or not DLK contributes to the regulation of this fundamental process in vivo is an intriguing question that remains to be addressed. Consequently, in the current project, we propose to examine the role of DLK in the epidermis by creating a mouse strain with a keratinocyte-specific conditional deletion of the DLK gene. It is anticipated that this approach will be extremely powerful for determining the role of DLK in epidermal differentiation, structure and maintenance. Such information may also have fundamental implications in the development of novel strategies for the treatment of certain skin disorders.