Floating the raft hypothesis: the roles of lipid rafts in B cell antigen receptor function

Cheng, Paul C.; Cherukuri, Anu; Dykstra, Michelle; Malapati, Sunil; Sproul, Tim W.; Chen, Michael R.; Pierce, Susan K.

doi:10.1006/smim.2000.0302

Cited by 61 publications

(55 citation statements)

References 24 publications

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“…Lipid rafts are specialized membrane microdomains which were initially defined by their insolubility in cold, non-ionic detergents and have been postulated to function as a signaling platforms for immune cell surface receptors such as TCT, BCR, and FcεR (Sheets et al, 1999;Janes et al, 2000;Cheng et al, 2001). More recently, an integral role of the membrane lipid rafts in proximal signaling events has been demonstrated for the TNFR family member such as CD40.…”

Section: Discussionmentioning

confidence: 99%

Lipid rafts are important for the association of RANK and TRAF6

Kwak²,

Le³

et al. 2003

Exp Mol Med

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A bstractRafts, cholesterol-and sphingolipid-rich m em brane m icrodom ains, have been show n to play an important role in im m une cell activation. M ore recently rafts w ere im plicated in the signal transduction by m em bers of the TNF receptor (TNFR) fam ily. In this study, we provide evidences that the raft m icrodom ain has a crucial role in RANK (receptor activator of NF-κB) signaling. W e found that the m ajority of the ectopically expressed RANK and substantial portion of endogenous TRAF2 and TRAF6 w ere detected in the low -density raft fractions. In addition, TRAF6 association w ith rafts was increased by RANKL stim ulation. The disruption of rafts blocked the TRAF6 translocation by RANK ligand and im peded the interaction betw een RANK and TRAF6. O ur observations dem onstrate that proper RANK signaling requires the function of raft m em brane m icrodom ains.

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Section: Discussionmentioning

confidence: 99%

Lipid rafts are important for the association of RANK and TRAF6

Kwak²,

Le³

et al. 2003

Exp Mol Med

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“…Previous studies implicate that lipid rafts play a role in both BCR signaling and trafficking (23,24). To determine the effect of Ag valency on the spatial relationship between the BCR and lipid rafts, the cellular distribution of the BCR and ganglioside G M1 was analyzed using immunofluorescence microscopy.…”

Section: Ag Valency and The Formation Of Bcr-signaling Microdomainsmentioning

confidence: 99%

Polyvalent Antigens Stabilize B Cell Antigen Receptor Surface Signaling Microdomains

Thyagarajan

Arunkumar

Song

2003

The Journal of Immunology

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The B cell Ag receptor (BCR) can distinguish subtle differences in Ag structure and trigger differential responses. In this study, we analyzed the effects of Ag valency on the signaling and Ag-targeting functions of the BCR. Although both paucivalent and polyvalent Ags induced the redistribution of the surface BCR into polarized caps, polyvalent Ag-induced BCR caps persisted. Ganglioside GM1, a lipid raft marker, and tyrosine-phosphorylated proteins, but not CD45 and transferrin receptor, were concentrated in BCR caps, suggesting BCR caps as surface-signaling microdomains. Prolonged BCR caps were concomitant with an increase in the level and duration of protein tyrosine phosphorylation and a reduction in BCR internalization and movement to late endosomes/lysosomes. Thus, Ag valency influences B cell responses by modulating the stability of BCR-signaling microdomains and BCR trafficking.

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“…The membrane lipid raft microdomain has been described as a functional platform for signaling of various stimuli and trafficking of signal receptor molecules (6,7). To further investigate the potential lipid raft localization of ORF5, 293T cells were transfected with empty vector or ORF5 expression vector.…”

Section: Resultsmentioning

confidence: 99%

“…Lipid rafts were isolated by floatation on discontinuous sucrose gradients (6,7). Briefly, 293T cells (five 10-cm-diameter dishes) were washed with ice-cold PBS and lysed for 30 min on ice in 1% Triton X-100 in TNEV (10 mM Tris-HCl [pH 7.5], 150 mM NaCl, 5 mM EDTA) containing phosphatase inhibitors and protease inhibitor cocktail (Roche, Indianapolis, Ind.).…”

Section: Rna Extraction and Reverse Transcriptase Pcr (Rt-pcr)mentioning

confidence: 99%

Modulation of T-Cell Receptor Signal Transduction by Herpesvirus Signaling Adaptor Protein

Lee

Chung

Cho

et al. 2004

Molecular and Cellular Biology

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Because of its central regulatory role, T-cell receptor (TCR) signal transduction is a common target of viruses. We report here the identification of a small signaling protein, ORF5, of the T-lymphotropic tumor virus herpesvirus saimiri (HVS). ORF5 is predicted to contain 89 to 91 amino acids with an amino-terminal myristoylation site and six SH2 binding motifs, showing structural similarity to cellular LAT (linker for activation of T cells). Sequence analysis showed that, despite extensive sequence variation, the myristoylation site and SH2 binding motifs were completely conserved among 13 different ORF5 isolates. Upon TCR stimulation, ORF5 was efficiently tyrosine phosphorylated and subsequently interacted with cellular SH2-containing signaling proteins Lck, Fyn, SLP-76, and p85 through its tyrosine residues. ORF5 expression resulted in the marked augmentation of TCR signal transduction activity, evidenced by increased cellular tyrosine phosphorylation, intracellular calcium mobilization, CD69 surface expression, interleukin-2 production, and activation of the NF-AT, NF-B, and AP-1 transcription factors. Despite its structural similarity to cellular LAT, however, ORF5 could only partially substitute for LAT function in TCR signal transduction. These results demonstrate that HVS utilizes a novel signaling protein, ORF5, to activate TCR signal transduction. This activation probably facilitates viral gene expression and, thereby, persistent infection.Upon engagement of the T-cell antigen receptor (TCR), many cellular proteins, including TCR subunits, adaptor proteins, and other effector molecules, are phosphorylated and subsequently are involved in the formation of molecular complexes at the site of contact with the antigen-presenting cells (33, 51, 54) The earliest signaling event following TCR engagement is the sequential activation of the non-receptor protein tyrosine kinases (PTKs) of the Src and Syk families. Activated Src family PTKs, Lck and Fyn, in T cells subsequently phosphorylate tyrosine residues within a consensus sequence termed the immunoreceptor tyrosine-based activation motif in the cytosolic tails of the TCR subunits. The phosphorylated immunoreceptor tyrosine-based activation motifs of TCR in turn recruit the Syk family PTKs ZAP70 and Syk through their Src homology 2 (SH2) domains (33). Together with Lck and Fyn, the ZAP70 and Syk kinases then promote the phosphorylation of many intracellular signaling molecules, including phospholipase C-␥1 (PLC-␥1), Cbl, Vav, LAT (linker for activation of T cells) and SLP-76 (SH2-containing leukocyte protein-76) (12,25,41,45,46,53). Phosphorylation of these cellular signaling molecules ultimately induces various cellular events such as cytoskeletal alteration, intracellular Ca ϩϩ influx, transcription factor activation, and cytokine/chemokine production (4,20,38,43,59).Two adaptor proteins, LAT and SLP-76, have been shown to be critical for the optimal activation of T cells and to function in linking proximal signaling events to distal downstream signaling ac...

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Floating the raft hypothesis: the roles of lipid rafts in B cell antigen receptor function

Cited by 61 publications

References 24 publications

Lipid rafts are important for the association of RANK and TRAF6

Lipid rafts are important for the association of RANK and TRAF6

Polyvalent Antigens Stabilize B Cell Antigen Receptor Surface Signaling Microdomains

Modulation of T-Cell Receptor Signal Transduction by Herpesvirus Signaling Adaptor Protein

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