Caveolin-1 a main structural protein constituent of caveolae plays an important role in the signal transduction endocytosis and cholesterol transport In addition caveolin-1 has conflictive role in the regulation of cell survival and death depending on intracellular signaling pathways The receptor tyrosine kinase TrkA has been known to Interact with caveolin-1 and exploits multiple functions such as cell survival death and differentiation In this report we investigated how TrkA-induced cell death signaling is regulated by caveolin-1 in both TrkA and caveolin-1 overexpressing stable U2OS cells Here we show that TrkA co-localizes with caveolin-1 mostly as a large aggresome around nucleus by confocal immunofluorescence microscopy Interestingly TrkA-mediated Bak cleavage was suppressed by caveolin-1 indicating an inhibition of TrkA-induced cell death signaling by caveolin-1 Moreover caveolin-1 altered TrkA modification including tyrosine-490 phosphorylation and unidentified cleavage(s) resulting in the inhibition of TrkA-Induced apoptotic cell death Our results suggest that caveolin-1 could suppress TrkA-mediated pleiotypic effects by altering TrkA modification via functional interaction (C) 2010 Elsevier Inc All rights reserved