The small heat-shock protein Hsp27 undergoes ERK-dependent phosphorylation and redistribution to the cytoskeleton in response to dual leucine zipper-bearing kinase expression.
Hsp27, a small heat-shock protein, has important roles in many cellular processes, including cytoskeleton dynamics, cell differentiation, and apoptosis. Its expression in normal epidermis correlates with differentiation; however, little is known about the regulatory mechanisms involved. In this study, we report that Hsp27 undergoes upregulation, phosphorylation, and redistribution to the cytoskeleton during the late phase of epidermal keratinocyte differentiation. Our results also show that the expression of the dual leucine zipper-bearing kinase (DLK), an upstream activator of the MAP kinase pathways, is sufficient by itself to induce Hsp27 phosphorylation, cell periphery localization, and redistribution to the insoluble protein fraction (cytoskeleton) in poorly differentiated keratinocytes. This redistribution correlates with the insolubilization of cornified envelope-associated proteins such as involucrin. Interestingly, the effects of DLK on Hsp27 were blocked by PD98059, a selective inhibitor of the extracellular signal-regulated protein kinase (ERK) pathway. Moreover, downregulation of Hsp27 by small interfering RNA in epithelial cells expressing DLK was accompanied by attenuated expression of involucrin in the cytoskeleton. Thus, these observations suggest that the DLK-ERK signaling pathway may act as a regulator of the interaction that occurs between Hsp27 and the cytoskeleton during the formation of the cornified cell envelope, a process conferring to the skin its crucial barrier function.
Robitaille
Hubert
H
Laboratoire de Recherche des Grands Brûlés/LOEX, Centre de recherche (FRSQ) du CHA de Québec, Québec, Québec, Canada.
Simard-Bisson
Carolyne
C
Larouche
Danielle
D
Tanguay
Robert M
RM
Blouin
Richard
R
Germain
Lucie
L
D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000201:enzymology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D018832:Molecular Chaperones; D010766:Phosphorylation / Q000502:physiology; D011498:Protein Precursors / Q000378:metabolism; D034622:RNA Interference; D023822:Tissue Engineering; D011503:Transglutaminases / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D011498:Protein Precursors; D049452:Green Fluorescent Proteins; C032253:involucrin; D011503:Transglutaminases; C105804:transglutaminase 1; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; C090757:mitogen-activated protein kinase kinase kinase 12