Compartmentalization of integrin alpha6beta4 signaling in lipid rafts

Details

Serval ID
serval:BIB_9993CFE4E5DF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Compartmentalization of integrin alpha6beta4 signaling in lipid rafts
Journal
Journal of Cell Biology
Author(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)
Publication state
Published
Issued date
09/2003
Volume
162
Number
7
Pages
1189-96
Notes
Journal Article
Research Support, U.S. Gov't, P.H.S. --- Old month value: Sep 29
Abstract
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.
Keywords
Amino Acid Sequence Animals Cell Compartmentation/*physiology Cells, Cultured Humans Integrin alpha6beta4/*metabolism Keratinocytes/*cytology/*metabolism Membrane Microdomains/*physiology Molecular Sequence Data Palmitic Acid/metabolism Rats Signal Transduction/physiology src-Family Kinases/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 9:34
Last modification date
20/08/2019 16:01
Usage data