The transmembrane adaptor protein NTAL limits mast cell chemotaxis toward prostaglandin E-2

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F18%3A00497556" target="_blank" >RIV/68378050:_____/18:00497556 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1126/scisignal.aao4354" target="_blank" >http://dx.doi.org/10.1126/scisignal.aao4354</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1126/scisignal.aao4354" target="_blank" >10.1126/scisignal.aao4354</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The transmembrane adaptor protein NTAL limits mast cell chemotaxis toward prostaglandin E-2

Popis výsledku v původním jazyce

Chemotaxis of mast cells is one of the crucial steps in their development and function. Non-T cell activation linker (NTAL) is a transmembrane adaptor protein that inhibits the activation of mast cells and B cells in a phosphorylation-dependent manner. Here, we studied the role of NTAL in the migration of mouse mast cells stimulated by prostaglandin E-2 (PGE(2)). Although PGE(2) does not induce the tyrosine phosphorylation of NTAL, unlike IgE immune complex antigens, we found that loss of NTAL increased the chemotaxis of mast cells toward PGE(2). Stimulation of mast cells that lacked NTAL with PGE(2) enhanced the phosphorylation of AKT and the production of phosphatidylinositol 3,4,5-trisphosphate. In resting NTAL-deficient mast cells, phosphorylation of an inhibitory threonine in ERM family proteins accompanied increased activation of beta 1-containing integrins, which are features often associated with increased invasiveness in tumors. Rescue experiments indicated that only full-length, wild-type NTAL restored the chemotaxis of NTAL-deficient cells toward PGE(2). Together, these data suggest that NTAL is a key inhibitor of mast cell chemotaxis toward PGE(2), which may act through the RHOA/ERM/beta 1-integrin and PI3K/AKT axes.

Název v anglickém jazyce

The transmembrane adaptor protein NTAL limits mast cell chemotaxis toward prostaglandin E-2

Popis výsledku anglicky

Chemotaxis of mast cells is one of the crucial steps in their development and function. Non-T cell activation linker (NTAL) is a transmembrane adaptor protein that inhibits the activation of mast cells and B cells in a phosphorylation-dependent manner. Here, we studied the role of NTAL in the migration of mouse mast cells stimulated by prostaglandin E-2 (PGE(2)). Although PGE(2) does not induce the tyrosine phosphorylation of NTAL, unlike IgE immune complex antigens, we found that loss of NTAL increased the chemotaxis of mast cells toward PGE(2). Stimulation of mast cells that lacked NTAL with PGE(2) enhanced the phosphorylation of AKT and the production of phosphatidylinositol 3,4,5-trisphosphate. In resting NTAL-deficient mast cells, phosphorylation of an inhibitory threonine in ERM family proteins accompanied increased activation of beta 1-containing integrins, which are features often associated with increased invasiveness in tumors. Rescue experiments indicated that only full-length, wild-type NTAL restored the chemotaxis of NTAL-deficient cells toward PGE(2). Together, these data suggest that NTAL is a key inhibitor of mast cell chemotaxis toward PGE(2), which may act through the RHOA/ERM/beta 1-integrin and PI3K/AKT axes.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Science Signaling

ISSN

1945-0877

e-ISSN

—

Svazek periodika

11

Číslo periodika v rámci svazku

556

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

—

Kód UT WoS článku

000450014800001

EID výsledku v databázi Scopus

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