The small heat shock protein Hsp27 undergoes ERK‐dependent phosphorylation, redistribution to the cell periphery and insolubilization in response to dual leucine zipper‐bearing kinase expression in human keratinocytes

Abstract

Hsp27 plays important roles in many cellular processes, including cytoskeleton dynamic, cell differentiation and apoptosis. Its expression in normal human epidermis correlates with differentiation. However, little is known about the regulatory mechanisms involved. In this study, we report that Hsp27 undergoes up‐regulation, phosphorylation, redistribution to the cytoskeleton and insolubilization during the late phase of epidermal keratinocyte differentiation. Our results also demonstrate that expression of dual leucine zipper‐bearing kinase (DLK), an upstream activator of the MAPKinase pathways, is alone sufficient to induce those modifications of Hsp27 in poorly differentiated normal human keratinocytes. Interestingly, the effects of DLK on Hsp27 were blocked by the PD98059, a selective inhibitor of the ERK pathway. Also, preliminary results indicate that knock down of Hsp27 using siRNA in HaCat cells expressing DLK decreases the amount of insoluble cornified envelope precursors such as involucrin. Thus, these observations suggest that the DLK‐ERK signaling pathway may act as a regulator of the interactions that occurs between Hsp27 and the cytoskeleton during formation of the cornified cell envelope.