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

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30102 - Immunology

Project

<a href="/en/project/GJ16-09208Y" target="_blank" >GJ16-09208Y: T cell receptor signaling and fate decisions made by peripheral T cells in homeostasis and during inflammation</a><br>

Continuities

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

Publication year

2018

Confidentiality

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

Name of the periodical

Nature Immunology

ISSN

1529-2908

e-ISSN

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Volume of the periodical

19

Issue of the periodical within the volume

7

Country of publishing house

US - UNITED STATES

Number of pages

9

Pages from-to

733-741

UT code for WoS article

000436341300018

EID of the result in the Scopus database

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