Lck promotes Zap70-dependent LAT phosphorylation by bridging Zap70 to LAT

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F18%3A00495490" target="_blank" >RIV/68378050:_____/18:00495490 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1038/s41590-018-0131-1" target="_blank" >http://dx.doi.org/10.1038/s41590-018-0131-1</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41590-018-0131-1" target="_blank" >10.1038/s41590-018-0131-1</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Lck promotes Zap70-dependent LAT phosphorylation by bridging Zap70 to LAT

Popis výsledku v původním jazyce

T cell-antigen receptor (TCR) signaling requires the sequential activities of the kinases Lck and Zap7O. Upon TCR stimulation, Lck phosphorylates the TCR, thus leading to the recruitment, phosphorylation, and activation of Zap7O. Lck binds and stabilizes phosho-Zap7O by using its SH2 domain, and Zap7O phosphorylates the critical adaptors LAT and SLP76, which coordinate downstream signaling. It is unclear whether phosphorylation of these adaptors occurs through passive diffusion or active recruitment. We report the discovery of a conserved proline-rich motif in LAT that mediates efficient LAT phosphorylation. Lck associates with this motif via its SH3 domain, and with phospho-Zap7O via its SH2 domain, thereby acting as a molecular bridge that facilitates the colocalization of Zap70 and LAT. Elimination of this proline-rich motif compromises TCR signaling and T cell development. These results demonstrate the remarkable multifunctionality of Lck, wherein each of its domains has evolved to orchestrate a distinct step in TCR signaling.

Název v anglickém jazyce

Lck promotes Zap70-dependent LAT phosphorylation by bridging Zap70 to LAT

Popis výsledku anglicky

T cell-antigen receptor (TCR) signaling requires the sequential activities of the kinases Lck and Zap7O. Upon TCR stimulation, Lck phosphorylates the TCR, thus leading to the recruitment, phosphorylation, and activation of Zap7O. Lck binds and stabilizes phosho-Zap7O by using its SH2 domain, and Zap7O phosphorylates the critical adaptors LAT and SLP76, which coordinate downstream signaling. It is unclear whether phosphorylation of these adaptors occurs through passive diffusion or active recruitment. We report the discovery of a conserved proline-rich motif in LAT that mediates efficient LAT phosphorylation. Lck associates with this motif via its SH3 domain, and with phospho-Zap7O via its SH2 domain, thereby acting as a molecular bridge that facilitates the colocalization of Zap70 and LAT. Elimination of this proline-rich motif compromises TCR signaling and T cell development. These results demonstrate the remarkable multifunctionality of Lck, wherein each of its domains has evolved to orchestrate a distinct step in TCR signaling.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

30102 - Immunology

Projekt

<a href="/cs/project/GJ16-09208Y" target="_blank" >GJ16-09208Y: Vliv signalizace T-buněčného receptoru na vývoj a diferenciaci periferních T-lymfocytů v homeostázi a při zánětu</a><br>

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

Nature Immunology

ISSN

1529-2908

e-ISSN

—

Svazek periodika

19

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

733-741

Kód UT WoS článku

000436341300018

EID výsledku v databázi Scopus

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