Caveolin-1 associates with TRAF2 to form a complex that is recruited to tumor necrosis factor receptors.
Tumor necrosis factor (TNF) receptor-associated factor (TRAF) 2 is an intracellular adapter protein, which, upon TNF stimulation, is directly recruited to the intracellular region of TNF receptor 2 (TNFR2) or indirectly, via TRADD, to the intracellular region of TNF receptor 1 (TNFR1). In cultured human umbilical vein endothelial cells, endogenous TRAF2 colocalizes with the membrane-organizing protein caveolin-1 at regions of enrichment subjacent to the plasma membrane as detected by confocal fluorescence microscopy. Both endogenous and transfected TRAF2 protein coimmunoprecipitate with caveolin-1 in the absence of ligand. Upon TNF treatment, the TRAF2-caveolin-1 complex transiently associates with TRADD, and upon overexpression of TNFR2, the TRAF2-caveolin-1 complex stably associates with and causes redistribution of this receptor as detected by confocal fluorescence microscopy. In human embryonic kidney 293 cells, which have minimal endogenous expression of caveolin-1, cotransfection of TRAF2 and caveolin-1 results in spontaneous association of these proteins which can further associate with and redistribute transfected TNFR2 molecules. The association of caveolin-1 with TNFR2 depends upon TRAF2. Cotransfection of caveolin-1 protein increases TRAF2 protein expression levels in HEK 293 cells, which correlates with enhancement of TNF and TRAF2 signaling, measured as transcription of a NF-kappaB promoter-reporter gene, although the caveolin-enhanced response to TNF is attenuated at higher caveolin levels. These findings suggest that intracellular distribution of activated TNF receptors may be regulated by caveolin-1 via its interaction with TRAF2.
Feng
X
X
Interdepartmental Program in Vascular Biology and Transplantation, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536-0812, USA.
Gaeta
M L
ML
Madge
L A
LA
Yang
J H
JH
Bradley
J R
JR
Pober
J S
JS
D015703:Antigens, CD / Q000378:metabolism*; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D014162:Transfection
D015703:Antigens, CD; C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D016328:NF-kappa B; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2