Caveolin-1 Associates with TRAF2 to Form a Complex That Is Recruited to Tumor Necrosis Factor Receptors

Feng, Xiao; Gaeta, Mary Lou; Madge, Lisa A.; Yang, Jason; Bradley, John R.; Pober, Jordan S.

doi:10.1074/jbc.m007116200

Cited by 87 publications

(69 citation statements)

References 38 publications

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“…Caveolin-1 has been previously found associated with TRAF2 but not with TNFR1, TNFR2, or TRADD in resting HUVECs. 39 A key difference from these earlier studies is that HUVECs, despite retaining expression of caveolin-1 and -2, no longer form caveolae. This may explain why the interaction of TNFR1 and caveolin-1 may be observed in EA.hy926 cells but not in HUVECs.…”

Section: Discussioncontrasting

confidence: 47%

Caveolae Participate in Tumor Necrosis Factor Receptor 1 Signaling and Internalization in a Human Endothelial Cell Line

D’Alessio¹,

Al‐Lamki²,

Bradley³

et al. 2005

The American Journal of Pathology

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105

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Caveolae are abundant in endothelial cells (ECs) in situ but markedly diminished in cultured cells, making it difficult to assess their role in cytokine signaling. We report here that the human EC line EA.hy926 retains an abundant caveolar system in culture. Tumor necrosis factor (TNF) receptor 1 (TNFR1/CD120a) was enriched in caveolae and co-immunoprecipitated with caveolin-1 from caveolae isolated from these cells. To further investigate the role(s) of caveolae in TNF signaling in ECs, cells were treated with methyl-␤-cyclodextrin to disrupt caveolae. Methyl-␤-cyclodextrin did not alter total cell surface expression of TNFR1 or TNF-induced degradation of IB␣, a measure of nuclear factor-B activation, but it did inhibit TNF-induced phosphorylation of Akt, a measure of phosphatidylinositol-3 kinase activation. Serum-induced phosphorylation of AKT was unaffected. Treatment with TNF induced disappearance of TNFR1 from caveolae and dissociation from caveolin-1 within 5 minutes. In contrast to transferrin receptor, internalized TNFR1 did not co-localize with clathrin, except possibly in the Golgi, at any time point examined. By 60 minutes of treatment with TNF, TNFR1 appeared in endosomes. We conclude that caveolae function in ECs to allow TNFR1 to activate phosphatidylinositol-3 kinase and Akt, perhaps through receptor cross talk, and that ligand-induced internalization and trafficking of TNFR1 to endosomes may originate directly from this compartment.

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Section: Discussioncontrasting

confidence: 47%

Caveolae Participate in Tumor Necrosis Factor Receptor 1 Signaling and Internalization in a Human Endothelial Cell Line

D’Alessio¹,

Al‐Lamki²,

Bradley³

et al. 2005

The American Journal of Pathology

Self Cite

105

View full text Add to dashboard Cite

show abstract

“…A similar view has also been proposed to explain the initial recruitment of the TCR complex into rafts and the subsequent formation of the so-called "immunological synapse" (36,37). Recent studies with CD120b have suggested that caveolin forms a complex with TNFR-associated factor 2 which in turn interacts with CD120b (38). However, it remains to be determined how the DD of CD120a promotes raft localization of CD120a and what role, if any, is played by the cytoskeleton.…”

Section: Discussionmentioning

confidence: 95%

Restricted Localization of the TNF Receptor CD120a to Lipid Rafts: A Novel Role for the Death Domain

Cottin

Doan

Riches

2002

The Journal of Immunology

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The TNF-α receptor, CD120a, has recently been shown to be localized to both plasma membrane lipid rafts and to the trans Golgi complex. Through a combination of both confocal microscopy and sucrose density gradient ultracentrifugation, we show that amino acid sequences located within the death domain (DD) of CD120a are both necessary and sufficient to promote the appropriate localization of the receptor to lipid rafts. Deletion of the DD (CD120a.Δ321-425) prevented the receptor from being targeted to lipid rafts and resulted in a uniform plasma membrane localization. A similar loss of raft localization was also observed following pairwise deletion of the six α-helices that comprise the DD. In all situations, the loss of the ability of CD120a to become localized to lipid rafts following mutagenesis was paralleled by a failure of the receptor to initiate apoptosis. Furthermore, introduction of the lpr mutation into CD120a (CD120a.L351N) also resulted in both a loss in the ability of the receptor to signal apoptosis and to be appropriately localized to rafts. In contrast to CD120a, CD120b, which lacks a DD, is mainly expressed in the bulk plasma membrane and to a lesser extent in lipid rafts, but is absent from the Golgi complex. However, a chimeric receptor in which the DD of CD120a was fused to the cytoplasmic domain of CD120b was predominantly localized to lipid rafts. Collectively, these findings suggest that in addition to its role in CD120a signaling, an appropriately folded and functionally active DD is required for the localization of the receptor to lipid rafts.

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“…In previous work, wild type Btk and the gain-of-function mutant, E41K, have been shown to efficiently translocate to the cell surface and localize predominantly in areas referred to as membrane ruffles or lamellipodia, structures known to be caused by robust actin polymerization (37). This finding is of great interest, because caveolin has also been reported to be focally enriched in regions located close to the plasma membrane (43).…”

Section: Tec Family Tyrosine Kinases Contain a Caveolin-bindingmentioning

confidence: 93%

Functional Interaction of Caveolin-1 with Bruton's Tyrosine Kinase and Bmx

Vargas¹,

Nore²,

Berglöf³

et al. 2002

Journal of Biological Chemistry

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Bruton's tyrosine kinase (Btk), a member of the Tec family of protein-tyrosine kinases, has been shown to be crucial for B cell development, differentiation, and signaling. Mutations in the Btk gene lead to X-linked agammaglobulinemia in humans and X-linked immunodeficiency in mice. Using a co-transfection approach, we present evidence here that Btk interacts physically with caveolin-1, a 22-kDa integral membrane protein, which is the principal structural and regulatory component of caveolae membranes. In addition, we found that native Bmx, another member of the Tec family kinases, is associated with endogenous caveolin-1 in primary human umbilical vein endothelial cells. Second, in transient transfection assays, expression of caveolin-1 leads to a substantial reduction in the in vivo tyrosine phosphorylation of both Btk and its constitutively active form, E41K. Furthermore, a caveolin-1 scaffolding peptide (amino acids 82-101) functionally suppressed the autokinase activity of purified recombinant Btk protein. Third, we demonstrate that mouse splenic B-lymphocytes express substantial amounts of caveolin-1. Interestingly, caveolin-1 was found to be constitutively phosphorylated on tyrosine 14 in these cells. The expression of caveolin-1 in B-lymphocytes and its interaction with Btk may have implications not only for B cell activation and signaling, but also for antigen presentation.

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Caveolin-1 Associates with TRAF2 to Form a Complex That Is Recruited to Tumor Necrosis Factor Receptors

Cited by 87 publications

References 38 publications

Caveolae Participate in Tumor Necrosis Factor Receptor 1 Signaling and Internalization in a Human Endothelial Cell Line

Caveolae Participate in Tumor Necrosis Factor Receptor 1 Signaling and Internalization in a Human Endothelial Cell Line

Restricted Localization of the TNF Receptor CD120a to Lipid Rafts: A Novel Role for the Death Domain

Functional Interaction of Caveolin-1 with Bruton's Tyrosine Kinase and Bmx

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