Caveolin 1-mediated regulation of receptor tyrosine kinase-associated phosphatidylinositol 3-kinase activity by ceramide
Authors: A Giaccia
W Zundel
L M Swiersz
Journal: Molecular and Cellular Biology (2000)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: proapoptotic stresses; phosphatidylinositol 3-kinase; PI(3)K; Akt survival pathway; acid-sphingomyelinase
Affiliations: Cancer Biology Program, Mayer Cancer Biology Research Laboratory, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California 94305-5468, USA.

Abstract:  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. 

Retracted: No

PubPeer comments:
 https: retractionwatch.com 2021 01 26 researcher-fired-for-including-an-author-not-involved-in-a-paper-says-colleague #more-121363  , 
 Retracted, see https: retractionwatch.com 2021 02 01 journal-pulls-two-studies-that-listed-an-author-without-his-permission for backgrounds. https: link.springer.com article 10.1007 s10586-018-1847-2 reports at the moment:  Article Not Found . , 
 The article is back now - redacted to remove Dr Cox. https: link.springer.com article 10.1007%2Fs10586-018-1847-2 According to the Retraction Note (bold text in the original),  The Editors-in-Chief have retracted this article.  After publication, it has come to the Editorsu2019 attention that the email address provided for Dr. David Cox as part of the submission did not belong to him. **The corresponding author and Dr. Cox have confirmed that Dr. Cox did not contribute to the article**. Dr David Coxu2019s name has been removed from the author list and his biographical information included in the article pdf has been redacted. Moreover, post-publication peer review found that the methods and results are inadequately described to support the conclusions presented in the article. The Editors-in-Chief therefore no longer have confidence in the reliability of the work presented. ,