Src-mediated caveolin-1 phosphorylation regulates intestinal epithelial restitution by altering Ca(2+) influx after wounding.
Am J Physiol Gastrointest Liver Physiol
; 306(8): G650-8, 2014 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-24557763
ABSTRACT
Early mucosal restitution occurs as a consequence of intestinal epithelial cell (IEC) migration to reseal superficial wounds, but its exact mechanism remains largely unknown. Caveolin-1 (Cav1), a major component associated with caveolar lipid rafts in the plasma membrane, is implicated in many aspects of cellular functions. This study determined if c-Src kinase (Src)-induced Cav1 phosphorylation promotes intestinal epithelial restitution after wounding by activating Cav1-mediated Ca(2+) signaling. Src directly interacted with Cav1, formed Cav1-Src complexes, and phosphorylated Cav1 in IECs. Inhibition of Src activity by its chemical inhibitor PP2 or suppression of the functional caveolin scaffolding domain by caveolin-scaffolding domain peptides prevented Cav1-Src interaction, reduced Cav1 phosphorylation, decreased Ca(2+) influx, and inhibited cell migration after wounding. Disruption of caveolar lipid raft microdomains by methyl-ß-cyclodextrin reduced Cav1-mediated Ca(2+) influx and repressed epithelial restitution. Moreover, Src silencing prevented subcellular redistribution of phosphorylated Cav1 in migrating IECs. These results indicate that Src-induced Cav1 phosphorylation stimulates epithelial restitution by increasing Cav1-mediated Ca(2+) signaling after wounding, thus contributing to the maintenance of gut mucosal integrity under various pathological conditions.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cálcio
/
Quinases da Família src
/
Caveolina 1
/
Mucosa Intestinal
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article