CD45 functions as a signaling gatekeeper in T cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F19%3A00511337" target="_blank" >RIV/68378050:_____/19:00511337 - isvavai.cz</a>

Výsledek na webu

<a href="https://stke.sciencemag.org/content/12/604/eaaw8151" target="_blank" >https://stke.sciencemag.org/content/12/604/eaaw8151</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1126/scisignal.aaw8151" target="_blank" >10.1126/scisignal.aaw8151</a>

Jazyk výsledku

angličtina

Název v původním jazyce

CD45 functions as a signaling gatekeeper in T cells

Popis výsledku v původním jazyce

T cells require the protein tyrosine phosphatase CD45 to detect and respond to antigen because it activates the Src family kinase Lck, which phosphorylates the T cell antigen receptor (TCR) complex. CD45 activates Lck by opposing the negative regulatory kinase Csk. Paradoxically, CD45 has also been implicated in suppressing TCR signaling by dephosphorylating the same signaling motifs within the TCR complex upon which Lck acts. We sought to reconcile these observations using chemical and genetic perturbations of the Csk/CD45 regulatory axis incorporated with computational analyses. Specifically, we titrated the activities of Csk and CD45 and assessed their influence on Lck activation, TCR-associated.-chain phosphorylation, and more downstream signaling events. Acute inhibition of Csk revealed that CD45 suppressed zeta-chain phosphorylation and was necessary for a regulatable pool of active Lck, thereby interconnecting the activating and suppressive roles of CD45 that tune antigen discrimination. CD45 suppressed signaling events that were antigen independent or induced by low-affinity antigen but not those initiated by high-affinity antigen. Together, our findings reveal that CD45 acts as a signaling ´gatekeeper,´ enabling graded signaling outputs while filtering weak or spurious signaling events.

Název v anglickém jazyce

CD45 functions as a signaling gatekeeper in T cells

Popis výsledku anglicky

T cells require the protein tyrosine phosphatase CD45 to detect and respond to antigen because it activates the Src family kinase Lck, which phosphorylates the T cell antigen receptor (TCR) complex. CD45 activates Lck by opposing the negative regulatory kinase Csk. Paradoxically, CD45 has also been implicated in suppressing TCR signaling by dephosphorylating the same signaling motifs within the TCR complex upon which Lck acts. We sought to reconcile these observations using chemical and genetic perturbations of the Csk/CD45 regulatory axis incorporated with computational analyses. Specifically, we titrated the activities of Csk and CD45 and assessed their influence on Lck activation, TCR-associated.-chain phosphorylation, and more downstream signaling events. Acute inhibition of Csk revealed that CD45 suppressed zeta-chain phosphorylation and was necessary for a regulatable pool of active Lck, thereby interconnecting the activating and suppressive roles of CD45 that tune antigen discrimination. CD45 suppressed signaling events that were antigen independent or induced by low-affinity antigen but not those initiated by high-affinity antigen. Together, our findings reveal that CD45 acts as a signaling ´gatekeeper,´ enabling graded signaling outputs while filtering weak or spurious signaling events.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

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

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

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

12

Číslo periodika v rámci svazku

604

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

aaw8151

Kód UT WoS článku

000492378200002

EID výsledku v databázi Scopus

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