Cell death-induced activation of epidermal growth factor receptor in keratinocytes: implications for restricting epidermal damage in dermatitis.
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Version: author
State: Public
Version: author
Serval ID
serval:BIB_DF547573566B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cell death-induced activation of epidermal growth factor receptor in keratinocytes: implications for restricting epidermal damage in dermatitis.
Journal
Journal of Investigative Dermatology
ISSN
0022-202X (Print)
ISSN-L
0022-202X
Publication state
Published
Issued date
2005
Volume
125
Number
1
Pages
134-142
Language
english
Abstract
Recent findings have implicated Fas/Fas ligand (FasL) in mediating the death of keratinocytes in spongiotic lesions. We asked whether dying keratinocytes could potentially initiate a protective response of the skin to limit the destruction of the epidermis in the spongiotic areas. In addition to apoptosis, treatment of keratinocyte cultures in vitro with FasL triggers a profound phoshorylation of the epidermal growth factor receptor (EGFR) and of its downstream effectors ERK and protein kinase B (PKB/Akt). Using a variety of inhibitors and blocking antibodies, we demonstrated that: (i) apoptosis is required for the generation of the signal(s) leading to the activation of EGFR, ERK, and Akt; (ii) the activation of EGFR, ERK, and Akt by FasL is indeed mediated by its bona fide receptor Fas; (iii) the activation of EGFR is essential for the subsequent activation of ERK and Akt; and (iv) apoptotic keratinocytes secrete soluble EGFR ligands (including amphiregulin) that are processed from membrane-bound proligand forms by metalloproteinase(s). Our findings demonstrate a potential mechanism for the restriction and repair of spongiotic damage in eczemas.
Keywords
Apoptosis, Cell Culture Techniques, Dermatitis/metabolism, Dermatitis/pathology, Fas Ligand Protein, Humans, Keratinocytes/metabolism, Membrane Glycoproteins/metabolism, Receptor, Epidermal Growth Factor/metabolism, Signal Transduction
Pubmed
Web of science
Open Access
Yes
Create date
19/01/2008 18:30
Last modification date
20/08/2019 17:03