IIntramolekulární regulace ZAP-70: analogie s receptorovými tyrosin kinasami

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F05%3A00023676" target="_blank" >RIV/68378050:_____/05:00023676 - isvavai.cz</a>

Výsledek na webu

—

DOI - Digital Object Identifier

—

Jazyk výsledku

angličtina

Název v původním jazyce

Intramolecular regulatory switch in ZAP-70: analogy with receptor tyrosine kinases

Popis výsledku v původním jazyce

ZAP-70 is a cytoplasmic tyrosine kinase required to couple the activated T cell antigen receptor to downstream signaling pathways. It contains two tandem SH2 domains separated from a C-terminal catalytic domain by the region termed Interdomain B. Interdomain B has striking regulatory effects on ZAP-70 function, but its deletion leads only to minor defects. To resolve this paradox we utilized the analogy with several receptor tyrosine kinases (RTK) which are in the resting state autoinhibited by the interaction between their kinase domain and tyrosine residues within their juxtamembrane region. Autoinhibition is released when these tyrosines become phosphorylated following receptor stimulation. Based on mutagenesis analysis we found that Interdomain B downregulates ZAP-70 catalytic activity in a similar manner as the juxtamembrane region of RTKs. This finding suggests that a general autoinhibitory mechanism employed by RTKs is also used by some cytoplasmic tyrosine-kinases.

Název v anglickém jazyce

Intramolecular regulatory switch in ZAP-70: analogy with receptor tyrosine kinases

Popis výsledku anglicky

ZAP-70 is a cytoplasmic tyrosine kinase required to couple the activated T cell antigen receptor to downstream signaling pathways. It contains two tandem SH2 domains separated from a C-terminal catalytic domain by the region termed Interdomain B. Interdomain B has striking regulatory effects on ZAP-70 function, but its deletion leads only to minor defects. To resolve this paradox we utilized the analogy with several receptor tyrosine kinases (RTK) which are in the resting state autoinhibited by the interaction between their kinase domain and tyrosine residues within their juxtamembrane region. Autoinhibition is released when these tyrosines become phosphorylated following receptor stimulation. Based on mutagenesis analysis we found that Interdomain B downregulates ZAP-70 catalytic activity in a similar manner as the juxtamembrane region of RTKs. This finding suggests that a general autoinhibitory mechanism employed by RTKs is also used by some cytoplasmic tyrosine-kinases.

Druh

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

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

—

Projekt

—

Návaznosti

Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2005

Kód důvěrnosti údajů

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

Název periodika

Molecular and Cellular Biology

ISSN

0270-7306

e-ISSN

—

Svazek periodika

25

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

4924-4933

Kód UT WoS článku

—

EID výsledku v databázi Scopus

—