Lipid Rafts Unite Signaling Cascades with Clathrin to Regulate BCR Internalization

Stoddart, Angela; Dykstra, Michelle; Brown, Bruce K.; Song, Wenxia; Brodsky, Frances M.

doi:10.1016/s1074-7613(02)00416-8

Cited by 203 publications

(245 citation statements)

References 48 publications

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“…The unexpected relation between tyrosine-phosphorylation and endocytosis, both of which are triggered by BCR activation, suggests that increased phosphorylation of endocytosis-related proteins plays a key role in BCR endocytosis. The clathrin-dependent pathway has been shown to be the primary pathway for ligand-induced BCR endocytosis, and raft structures appear to be required for efficient phosphorylation of clathrin heavy chain [21,33]. Tyrosine-phosphorylation of clathrin heavy chain is induced by an SRC-type protein kinase in response to stimulation of various receptor types, and the level of phosphorylation correlates with the rate of receptor internalization [21,[34][35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Large‐scale proteomic analysis of tyrosine‐phosphorylation induced by T‐cell receptor or B‐cell receptor activation reveals new signaling pathways

et al. 2009

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Activation of the T-cell receptor (TCR) and that of the B-cell receptor (BCR) elicits tyrosinephosphorylation of proteins that belongs to similar functional categories, but result in distinct cellular responses. Large-scale analyses providing an overview of the signaling pathways downstream of TCR or BCR have not been described, so it has been unclear what components of these pathways are shared and which are specific. We have now performed a systematic analysis and provide a comprehensive list of tyrosine-phosphorylated proteins (PY proteome) with quantitative data on their abundance in T cell, B cell, and nonlymphoid cell lines. Our results led to the identification of novel tyrosine-phosphorylated proteins and signaling pathways not previously implicated in immunoreceptor signal transduction, such as clathrin, zonula occludens 2, eukaryotic translation initiation factor 3, and RhoH, suggesting that TCR or BCR signaling may be linked to downstream processes such as endocytosis, cell adhesion, and translation. Thus comparative and quantitative studies of tyrosine-phosphorylation have the potential to expand knowledge of signaling networks and to promote understanding of signal transduction at the system level.

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Section: Discussionmentioning

confidence: 99%

Large‐scale proteomic analysis of tyrosine‐phosphorylation induced by T‐cell receptor or B‐cell receptor activation reveals new signaling pathways

et al. 2009

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“…This is similar to the endocytosis of soluble antigen, which also requires CCPs 124 . The endocytosis of antigen depends on SRC-family kinases 125 , BTK 126 , activation of the ARP2/3 complex through WAS, WASL, and WIPF1 7,35,60 and linkage of CCPs to actin by DBNL 127 . However, the endocytic mechanism may not be identical to that involving canonical CCPs as it requires RAC1 and RAC2, but not the typical regulator of actin polymerization in CCPs, CDC42 50 .…”

Section: [H1] Cytoskeletal Regulation Of Bcr Signallingmentioning

confidence: 99%

Cytoskeletal control of B cell responses to antigens

Tolar

2017

Nat Rev Immunol

123

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The actin cytoskeleton is essential for cell mechanics and has increasingly been implicated in the regulation of cell signalling. In B cells, the actin cytoskeleton couples extensively to B cell receptor (BCR) signalling pathways and its defects can either enhance or suppress B cell activation. Recent insights from single-cell imaging and biophysical techniques suggest that actin orchestrates BCR signalling at the plasma membrane through effects on protein diffusion, and that it regulates antigen discrimination through the biomechanics of immune synapses. These mechanical functions also play a role in the adaptation of B cell subsets to specialized tasks during antibody responses.3

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“…The 2R.50 T cells express MHC class II (I-A d )-restricted TCR specific for rabbit IgG and were maintained and used as previously described (34,35). The LK35.2 B cell transfectant (HyHEL10), which expresses a hen egg lysozyme (HEL)-specific IgM BCR, and 2G7 T cells, which express a MHC class II (I-E k )-restricted TCR specific for HEL [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] , were gifts from F. Batista (Medical Research Laboratory of Molecular Biology, Cambridge, U.K.) and were maintained and used as previously described (36).…”

Section: Cellsmentioning

confidence: 99%

“…Activation of Src family kinases, particularly Lyn, can regulate BCR internalization in some systems (7)(8)(9), perhaps via phosphorylation of clathrin H chain (10) and/or the adaptor protein Bam32 (11). Subsequent sorting of internalized BCR-Ag complexes into late endosomes and development of mature MHC class II-enriched compartment (MIIC) 3 (12)(13)(14) serve to quantitatively enhance generation of peptide-MHC complexes (15), and may promote expression of peptide-MHC complexes in a functional conformation capable of activating Ag-specific T cells and acting as a signal transduction unit for the B cell (16).…”

mentioning

confidence: 99%

Requirement for Phosphoinositide 3-Kinase p110δ Signaling in B Cell Antigen Receptor-Mediated Antigen Presentation

Al‐Alwan

Okkenhaug

Vanhaesebroeck

et al. 2007

The Journal of Immunology

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The BCR serves to both signal cellular activation and enhance uptake and presentation of Ags by B cells; however, the intracellular signaling mechanisms linking the BCR to Ag presentation functions have been controversial. PI3Ks are critical signaling enzymes controlling many cellular processes, with the p110δ isoform playing a critical role in BCR signaling. In this study, we used pharmacological and genetic approaches to evaluate the role of p110δ signaling in Ag presentation by primary B lymphocytes. It was found that activation of allogeneic T cells is significantly reduced when B cells are pretreated with global PI3K inhibitors, but was intact when p110δ signaling was specifically inactivated. In contrast, inactivation of p110δ significantly impaired the ability of B cells to activate T cells in a BCR-mediated Ag uptake and presentation model. Prestimulation of p110δ-inactivated B cells with anti-CD40 or LPS could not rescue their BCR-mediated Ag presentation ability to normal levels. p110δ signaling was required for efficient presentation of either anti-Ig or protein Ag via a lysozyme-specific BCR. p110δ-inactivated B cells were able to internalize Ag normally, and no defects in association of Ag with lysosome-associated membrane protein 1+ late endosomes were observed; however, these cells were less effective in forming polarized conjugates with Ag-specific T cells. Our data demonstrate a role for p110δ signaling in B cell Ag presentation function, implicating 3-phosphoinositides and their targets in the latter stages of this process.

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Lipid Rafts Unite Signaling Cascades with Clathrin to Regulate BCR Internalization

Cited by 203 publications

References 48 publications

Large‐scale proteomic analysis of tyrosine‐phosphorylation induced by T‐cell receptor or B‐cell receptor activation reveals new signaling pathways

Large‐scale proteomic analysis of tyrosine‐phosphorylation induced by T‐cell receptor or B‐cell receptor activation reveals new signaling pathways

Cytoskeletal control of B cell responses to antigens

Requirement for Phosphoinositide 3-Kinase p110δ Signaling in B Cell Antigen Receptor-Mediated Antigen Presentation

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