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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F16%3A00471873" target="_blank" >RIV/68378050:_____/16:00471873 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1128/MCB.00064-16" target="_blank" >http://dx.doi.org/10.1128/MCB.00064-16</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1128/MCB.00064-16" target="_blank" >10.1128/MCB.00064-16</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

Aggregation of the high-affinity receptor for IgE (Fc epsilon RI) 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 Fc epsilon RI-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. Fc epsilon RI-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-Fc epsilon RI complexes; this may be related to our finding that Gal3 is a positive regulator of Fc epsilon RI 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 Fc epsilon RI-mediated signaling events in mast cells.

Název v anglickém jazyce

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

Popis výsledku anglicky

Aggregation of the high-affinity receptor for IgE (Fc epsilon RI) 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 Fc epsilon RI-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. Fc epsilon RI-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-Fc epsilon RI complexes; this may be related to our finding that Gal3 is a positive regulator of Fc epsilon RI 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 Fc epsilon RI-mediated signaling events in mast cells.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

—

Projekt

<a href="/cs/project/GBP302%2F12%2FG101" target="_blank" >GBP302/12/G101: Molekulární mechanismy signalizace receptory leukocytů - jejich role ve zdraví a nemocích.</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecular and Cellular Biology

ISSN

0270-7306

e-ISSN

—

Svazek periodika

36

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

17

Strana od-do

1366-1382

Kód UT WoS článku

000374110900005

EID výsledku v databázi Scopus

—