Compartmentalization of integrin alpha6beta4 signaling in lipid rafts.

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Etat: Public
Version: Final published version
Licence: Non spécifiée
ID Serval
serval:BIB_9993CFE4E5DF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Compartmentalization of integrin alpha6beta4 signaling in lipid rafts.
Périodique
The Journal of cell biology
Auteur⸱e⸱s
Gagnoux-Palacios L., Dans M., van't Hof W., Mariotti A., Pepe A., Meneguzzi G., Resh M.D., Giancotti F.G.
ISSN
0021-9525 (Print)
ISSN-L
0021-9525
Statut éditorial
Publié
Date de publication
29/09/2003
Peer-reviewed
Oui
Volume
162
Numéro
7
Pages
1189-1196
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Résumé
Integrin alpha6beta4 signaling proceeds through Src family kinase (SFK)-mediated phosphorylation of the cytoplasmic tail of beta4, recruitment of Shc, and activation of Ras and phosphoinositide-3 kinase. Upon cessation of signaling, alpha6beta4 mediates assembly of hemidesmosomes. Here, we report that part of alpha6beta4 is incorporated in lipid rafts. Metabolic labeling in combination with mutagenesis indicates that one or more cysteine in the membrane-proximal segment of beta4 tail is palmitoylated. Mutation of these cysteines suppresses incorporation of alpha6beta4 in lipid rafts, but does not affect alpha6beta4-mediated adhesion or assembly of hemidesmosomes. The fraction of alpha6beta4 localized to rafts associates with a palmitoylated SFK, whereas the remainder does not. Ligation of palmitoylation-defective alpha6beta4 does not activate SFK signaling to extracellular signal-regulated kinase and fails to promote keratinocyte proliferation in response to EGF. Thus, compartmentalization in lipid rafts is necessary to couple the alpha6beta4 integrin to a palmitoylated SFK and promote EGF-dependent mitogenesis.
Mots-clé
Amino Acid Sequence, Animals, Cell Compartmentation/physiology, Cells, Cultured, Humans, Integrin alpha6beta4/metabolism, Keratinocytes/cytology, Keratinocytes/metabolism, Membrane Microdomains/physiology, Molecular Sequence Data, Palmitic Acid/metabolism, Rats, Signal Transduction/physiology, src-Family Kinases/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/01/2008 9:34
Dernière modification de la notice
09/08/2024 13:13
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