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

我们研究项目的目标是了解蛋白激酶在控制细胞生长、细胞分化和细胞死亡中的作用。这是特别有趣的，因为蛋白激酶功能的改变可以导致一系列缺陷，从发育异常到许多疾病，包括癌症。对蛋白激酶的全面了解可能有助于我们找到控制这些疾病的新方法。在NSERC的支持下，我们研究了双亮氨酸拉链激酶（DLK）的作用和特异性，DLK是一种丝氨酸/苏氨酸激酶，作为应激反应的c-Jun n端激酶的上游激活剂。通过使用分子和细胞生物学方法，我们的实验室最近积累了支持DLK在调节角质形成细胞（表皮的主要细胞类型）的终端分化中的作用的证据。DLK是否参与体内这一基本过程的调节是一个有趣的问题，仍有待解决。因此，在当前的项目中，我们建议通过创建具有角化细胞特异性条件缺失DLK基因的小鼠品系来研究DLK在表皮中的作用。预计这种方法将非常有力地确定DLK在表皮分化、结构和维持中的作用。这些信息也可能对开发治疗某些皮肤疾病的新策略具有根本意义。

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.