Detergent-Resistant Membrane Domains Are Required for Mast Cell Activation but Dispensable for Tyrosine Phosphorylation upon Aggregation of the High Affinity Receptor for IgE

2001 ◽  
Vol 129 (6) ◽  
pp. 861-868 ◽  
Author(s):  
T. Yamashita ◽  
T. Yamaguchi ◽  
K. Murakami ◽  
S. Nagasawa
Keyword(s):  
Mast Cell ◽  
Tyrosine Phosphorylation ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Membrane Domains ◽  
High Affinity ◽  
High Affinity Receptor ◽  
Affinity Receptor ◽  
Detergent Resistant Membrane

scholarly journals WIP Regulates Signaling via the High Affinity Receptor for Immunoglobulin E in Mast Cells

2004 ◽  
Vol 199 (3) ◽  
pp. 357-368 ◽  
Author(s):  
Alexander Kettner ◽  
Lalit Kumar ◽  
Inés M. Antón ◽  
Yoji Sasahara ◽  
Miguel de la Fuente ◽  
...  
Keyword(s):  
Mast Cells ◽  
Actin Cytoskeleton ◽  
Cell Activation ◽  
Immunoglobulin E ◽  
Mast Cell Activation ◽  
Interacting Protein ◽  
High Affinity ◽  
High Affinity Receptor ◽  
Affinity Receptor ◽  
Cytoskeleton Rearrangement

Wiskott-Aldrich syndrome protein–interacting protein (WIP) stabilizes actin filaments and is important for immunoreceptor-mediated signal transduction leading to actin cytoskeleton rearrangement in T and B cells. Here we report a role for WIP in signaling pathways downstream of the high affinity receptor for immunoglobulin (Ig)E (FcϵRI) in mast cells. WIP-deficient bone marrow–derived mast cells (BMMCs) were impaired in their capacity to degranulate and secrete interleukin 6 after FcϵRI ligation. Calcium mobilization, phosphorylation of Syk, phospholipase C-g2, and c-Jun NH2-terminal kinase were markedly decreased in WIP-deficient BMMCs. WIP was found to associate with Syk after FcϵRI ligation and to inhibit Syk degradation as evidenced by markedly diminished Syk levels in WIP-deficient BMMCs. WIP-deficient BMMCs exhibited no apparent defect in their subcortical actin network and were normal in their ability to form protrusions when exposed to an IgE-coated surface. However, the kinetics of actin changes and the cell shape changes that follow FcϵRI signaling were altered in WIP-deficient BMMCs. These results suggest that WIP regulates FcϵRI-mediated mast cell activation by regulating Syk levels and actin cytoskeleton rearrangement.

scholarly journals New Regulatory Roles of Galectin-3 in High-Affinity IgE Receptor Signaling

2016 ◽  
Vol 36 (9) ◽  
pp. 1366-1382 ◽  
Author(s):  
Monika Bambouskova ◽  
Iva Polakovicova ◽  
Ivana Halova ◽  
Gautam Goel ◽  
Lubica Draberova ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Mast Cell Degranulation ◽  
Negative Regulator ◽  
Mast Cell Activation ◽  
High Affinity ◽  
Galectin 3 ◽  
High Affinity Receptor ◽  
High Affinity Ige Receptor

Aggregation of the high-affinity receptor for IgE (FcεRI) in mast cells initiates activation events that lead to degranulation and release of inflammatory mediators. To better understand the signaling pathways and genes involved in mast cell activation, we developed a high-throughput mast cell degranulation assay suitable for RNA interference experiments using lentivirus-based short hairpin RNA (shRNA) delivery. We tested 432 shRNAs specific for 144 selected genes for effects on FcεRI-mediated mast cell degranulation and identified 15 potential regulators. In further studies, we focused on galectin-3 (Gal3), identified in this study as a negative regulator of mast cell degranulation. FcεRI-activated cells with Gal3 knockdown exhibited upregulated tyrosine phosphorylation of spleen tyrosine kinase and several other signal transduction molecules and enhanced calcium response. We show that Gal3 promotes internalization of IgE-FcεRI complexes; this may be related to our finding that Gal3 is a positive regulator of FcεRI ubiquitination. Furthermore, we found that Gal3 facilitates mast cell adhesion and motility on fibronectin but negatively regulates antigen-induced chemotaxis. The combined data indicate that Gal3 is involved in both positive and negative regulation of FcεRI-mediated signaling events in mast cells.

scholarly journals Dermal Mast Cell Activation by Autoantibodies Against the High Affinity IgE Receptor in Chronic Urticaria

1996 ◽  
Vol 106 (5) ◽  
pp. 1001-1006 ◽  
Author(s):  
Naomasa Niimi ◽  
David M. Francis ◽  
Faiz Kermani ◽  
Brigid F. O'Donnell ◽  
Michihiro Hide ◽  
...  
Keyword(s):  
Mast Cell ◽  
Chronic Urticaria ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Ige Receptor ◽  
High Affinity ◽  
High Affinity Ige Receptor

Negative regulation of FcϵRI-mediated mast cell activation by a ubiquitin-protein ligase Cbl-b

Blood ◽  
2004 ◽  
Vol 103 (5) ◽  
pp. 1779-1786 ◽  
Author(s):  
Xiujuan Qu ◽  
Kiyonao Sada ◽  
Shinkou Kyo ◽  
Koichiro Maeno ◽  
S. M. Shahjahan Miah ◽  
...  
Keyword(s):  
Mast Cell ◽  
Tyrosine Phosphorylation ◽  
Gene Transcription ◽  
Lipid Raft ◽  
Cell Activation ◽  
Immunoglobulin E ◽  
Negative Regulator ◽  
Mast Cell Activation ◽  
Cytokine Gene ◽  
Ubiquitin Protein Ligase

AbstractAggregation of the high-affinity immunoglobulin E (IgE) receptor (FcϵRI) on mast cells induces a number of biochemical events, including protein-tyrosine phosphorylation leading to degranulation and multiple cytokine gene transcription. Here, we have demonstrated that a second member of the Cbl family of ubiquitin-protein ligase Cbl-b translocates into the lipid raft after FcϵRI engagement. Overexpression of Cbl-b in the lipid raft inhibits FcϵRI-mediated degranulation and cytokine gene transcription through the distinct mechanism. A point mutation of Cys373 in the RING finger domain of Cbl-b abrogates the suppression of FcϵRI-mediated degranulation but not cytokine gene transcription. The antigen-induced tyrosine phosphorylation of FcϵRI, Syk, phospholipase C-γ (PLC-γ), activation of c-Jun N-terminal kinase (JNK), extracellular signal regulated kinase (ERK), inhibitor of nuclear factor κB kinase (IKK), and Ca++ influx were all suppressed in the cells overexpressing Cbl-b in the lipid raft. In particular, the expression amount of Gab2 protein and thereby its FcϵRI-mediated tyrosine phosphorylation were dramatically down-regulated by ubiquitin-protein ligase activity of Cbl-b. These results suggest that Cbl-b is a negative regulator of both Lyn-Syk-LAT and Gab2mediated complementary signaling pathways in FcϵRI-mediated mast cell activation.

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