c-Abl is required for oxidative stress-induced phosphorylation of caveolin-1 on tyrosine 14.
Caveolin-1 is phosphorylated at tyrosine 14 in response to cellular stress. Tyrosine 14 is a consensus Abl phosphorylation site suggesting that caveolin-1 may be an Abl substrate. We report here that expression of c-Abl is required for oxidative stress-induced caveolin-1 phosphorylation. In contrast, c-Src expression is not required. Phosphocaveolin is one of only two phosphotyrosine signals missing in lysates from the Abl(-/-) cells, indicating that these cells still respond to oxidative stress. Oxidative stress-induced tyrosine phosphorylation of caveolin-1 occurs only at the Abl site, tyrosine 14. Caveolin-1 is also a major phosphotyrosine signal detected in cells over-expressing c-Abl. Our results show that Abl activation leads to phosphorylation of caveolin-1 on tyrosine 14. Both Abl and caveolin have been linked to the actin cytoskeleton, and oxidative stress-induced phosphocaveolin is enriched at focal contacts. This suggests that phosphocaveolin regulates these structures, perhaps through recruiting and activating SH2-domain proteins such as Csk.
Sanguinetti
Amy R
AR
Department of Biochemistry, University of Nevada, Mail Stop 330, Reno, NV 89557, USA.
Mastick
Cynthia Corley
CC
D000818:Animals; D021941:Caveolae / Q000201:enzymology; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D022001:Focal Adhesions / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics* / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D018909:src Homology Domains / Q000502:physiology
C495540:CAV1 protein, human; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D022461:Caveolins; D010750:Phosphoproteins; D014443:Tyrosine; D016315:Proto-Oncogene Proteins c-abl