The mitogen-activated protein kinase kinase kinase dual leucine zipper-bearing kinase (DLK) acts as a key regulator of keratinocyte terminal differentiation.

Auteur(s): Robitaille, Hubert; Proulx, Roxanne; Robitaille, Karine; Blouin, RichardGermain, LucieGermain, Lucie
Résumé: In the skin, epithelial cells undergo a terminal differentiation program leading to the formation of the stratum corneum. Although it is expected that the last phases of this process must be tightly regulated since it results in cell death, the signaling pathways involved in this induction remain ill defined. We now report that a single kinase, the mitogen-activated protein kinase kinase kinase dual leucine zipper-bearing kinase (DLK), acts in the epidermis to promote the terminal differentiation of human keratinocytes. In support of this notion, we showed that DLK expression was restricted to the granular layer in situ. In addition, cultured keratinocytes infected with a recombinant adenovirus expressing DLK exhibited morphological and biochemical changes, including a suprabasal localization, altered cell shape, compacted cytoplasm, DNA fragmentation, and the up-regulation of filaggrin, that are reminiscent of a terminally differentiated phenotype. Moreover the expression of wild-type DLK in keratinocytes stimulated transglutaminase activity and the consequent formation of the cornified cell envelope, while a kinase-inactive variant of DLK did not. Together these results identify DLK as a signaling molecule implicated in the regulation of keratinocyte terminal differentiation and cornification.
Type de document: Article de recherche
Date de publication: 28 janvier 2005
Date de la mise en libre accès: 26 janvier 2018
Version du document: VoR
Lien permanent:
Ce document a été publié dans: The Journal of biological chemistry, Vol. 280 (13), 12732-12741 (2005)
American Society for Biochemistry and Molecular Biology
Autre version disponible: 10.1074/jbc.M411619200
Collection :Articles publiés dans des revues avec comité de lecture

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