Caveolin-1 inhibits TrkA-induced cell death by influencing on TrkA modification associated with tyrosine-490 phosphorylation.
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.
Department of Biochemistry, Gyeongsang National University, School of Medicine, Jinju, South Korea.
Eun Joo
EJ
Jung
Choong Won
CW
Kim
D017209:Apoptosis; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D020932:Nerve Growth Factor / Q000494:pharmacology; D010766:Phosphorylation; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism
D051242:Caveolin 1; D014443:Tyrosine; D020932:Nerve Growth Factor; D020917:Receptor, trkA