Caveolin 1-Mediated Regulation of Receptor Tyrosine Kinase-Associated Phosphatidylinositol 3-Kinase Activity by Ceramide
AUTOR(ES)
Zundel, Wayne
FONTE
American Society for Microbiology
RESUMO
Previous studies have indicated that proapoptotic stresses downregulate the phosphatidylinositol 3-kinase [PI(3)K]/Akt survival pathway via the activation of acid-sphingomyelinase (A-SMase) and ceramide production. Ceramide induces apoptosis and inhibits PI(3)K activity without altering expression, association, or phosphorylation of receptors, adapter proteins, or PI(3)K subunits. PI(3)K inhibition by ceramide is associated with recruitment of caveolin 1 to PI(3)K-associated receptor complexes within lipid raft microdomains. Overexpression of caveolin 1 alone is sufficient to alter PI(3)K activity and sensitizes fibroblasts to ceramide-induced cell death. Most importantly, antisense expression of caveolin 1 dramatically reduces ceramide-induced PI(3)K deregulation and results in a loss-of-function stress response similar to that in A-SMase-deficient cells. Stress-induced recruitment of caveolin 1 to receptor complexes was found to be dependent on A-SMase since cell lines deficient in A-SMase did not exhibit caveolin 1 association with PI(3)K receptor complexes. Thus, a genetic link between A-SMase activation and caveolin 1-induced inhibition of PI(3)K activity exists. These results led us to propose that stress-induced changes in raft microdomains lead to altered receptor tyrosine kinase signal transduction through the modulation of caveolin 1 by ceramide.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=85322Documentos Relacionados
- Control of Meristem Development by CLAVATA1 Receptor Kinase and Kinase-Associated Protein Phosphatase Interactions1
- β2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein
- The Arabidopsis kinase-associated protein phosphatase controls internalization of the somatic embryogenesis receptor kinase 1
- The Endothelial Receptor Tyrosine Kinase Tie1 Activates Phosphatidylinositol 3-Kinase and Akt To Inhibit Apoptosis
- NMR structure of the forkhead-associated domain from the Arabidopsis receptor kinase-associated protein phosphatase
