Nová negativní regulační funkce fosfoproteinu asociovaného s mikrodoménami obohacenými glykosfingolipidy: blokování aktivace Ras

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F07%3A00085150" target="_blank" >RIV/68378050:_____/07:00085150 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

A novel negative regulatory function of the phosphoprotein associated with glycosphingolipid-enriched microdomains: blocking Ras activation

Popis výsledku v původním jazyce

Analysis of anergic T cells revealed that adaptor protein PAG is hyperphosphorylated at the Csk binding site, leading to enhanced Csk recruitment and inhibitory tyrosine phosphorylation within Fyn. This together with enhanced phosphorylation of a tyrosine within the SH2 domain of Fyn leads to the formation of a hyperactive conformation, thus explaining the enhanced Fyn kinase activity. In addition, we have also identified the formation of a multiprotein complex containing PAG, Fyn, Sam68, and RasGAP instimulated T cells. PAG-Fyn overexpression is sufficient to suppress Ras activation in Jurkat T cells and this activity is independent of Csk binding. Thus, in addition to negatively regulating Src family kinases by recruiting Csk, PAG also negatively regulates Ras by recruiting RasGAP to the membrane. Finally, by knocking down PAG, both enhanced Src kinase activity and Ras activation was demonstrated, thereby establishing PAG as an important negative regulator of T-cell activation.

Název v anglickém jazyce

A novel negative regulatory function of the phosphoprotein associated with glycosphingolipid-enriched microdomains: blocking Ras activation

Popis výsledku anglicky

Analysis of anergic T cells revealed that adaptor protein PAG is hyperphosphorylated at the Csk binding site, leading to enhanced Csk recruitment and inhibitory tyrosine phosphorylation within Fyn. This together with enhanced phosphorylation of a tyrosine within the SH2 domain of Fyn leads to the formation of a hyperactive conformation, thus explaining the enhanced Fyn kinase activity. In addition, we have also identified the formation of a multiprotein complex containing PAG, Fyn, Sam68, and RasGAP instimulated T cells. PAG-Fyn overexpression is sufficient to suppress Ras activation in Jurkat T cells and this activity is independent of Csk binding. Thus, in addition to negatively regulating Src family kinases by recruiting Csk, PAG also negatively regulates Ras by recruiting RasGAP to the membrane. Finally, by knocking down PAG, both enhanced Src kinase activity and Ras activation was demonstrated, thereby establishing PAG as an important negative regulator of T-cell activation.

Druh

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

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

<a href="/cs/project/1M0506" target="_blank" >1M0506: Centrum molekulární a buněčné imunologie</a><br>

Návaznosti

Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2007

Kód důvěrnosti údajů

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

Název periodika

Blood

ISSN

0006-4971

e-ISSN

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Svazek periodika

110

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

596-605

Kód UT WoS článku

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EID výsledku v databázi Scopus

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