Cell death-induced activation of epidermal growth factor receptor in keratinocytes: implications for restricting epidermal damage in dermatitis.

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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
Author(s)
Iordanov M.S., Sundholm A.J., Simpson E.L., Hanifin J.M., Ryabinina O.P., Choi R.J., Korcheva V.B., Schneider P., Magun B.E.
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 17:30
Last modification date
20/08/2019 16:03
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