About: Grb2 and the non-T cell activation linker NTAL constitute a Ca(2+)-regulating signal circuit in B lymphocytes

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About: Grb2 and the non-T cell activation linker NTAL constitute a Ca(2+)-regulating signal circuit in B lymphocytes Goto Sponge NotDistinct Permalink

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
Description	Activation of the B cell antigen receptor triggers phosphorylation of cytoplasmic and transmembrane adaptor proteins such as SLP-65 and NTAL, respectively. Specific phosphoacceptor sites in SLP-65 serve as docking sites for Ca(2+)-mobilizing enzymes Btk and PLC-gamma2. Phosphorylated NTAL recruits the Grb2 linker, but downstream signaling cascades are unclear. We now show that receptor-induced tyrosine phosphorylation of NTAL and concomitant Grb2 complex formation critically modulate the Ca(2+) response without affecting SLP-65 and PLC-gamma2 phosphorylation. Grb2 turned out to play a negative regulatory role, which appears to be eliminated upon binding to NTAL. This allows for a sustained release of intracellular Ca(2+) and is mandatory for subsequent entry of Ca(2+) from extracellular sources. Thus, elevation of Ca(2+) is regulated by at least two signaling modules, the B cell-specific Ca(2+) initiation complex comprising SLP-65, Btk, and PLC-gamma2 and the more ubiquitously expressed NTAL/Grb2 c... Activation of the B cell antigen receptor triggers phosphorylation of cytoplasmic and transmembrane adaptor proteins such as SLP-65 and NTAL, respectively. Specific phosphoacceptor sites in SLP-65 serve as docking sites for Ca(2+)-mobilizing enzymes Btk and PLC-gamma2. Phosphorylated NTAL recruits the Grb2 linker, but downstream signaling cascades are unclear. We now show that receptor-induced tyrosine phosphorylation of NTAL and concomitant Grb2 complex formation critically modulate the Ca(2+) response without affecting SLP-65 and PLC-gamma2 phosphorylation. Grb2 turned out to play a negative regulatory role, which appears to be eliminated upon binding to NTAL. This allows for a sustained release of intracellular Ca(2+) and is mandatory for subsequent entry of Ca(2+) from extracellular sources. Thus, elevation of Ca(2+) is regulated by at least two signaling modules, the B cell-specific Ca(2+) initiation complex comprising SLP-65, Btk, and PLC-gamma2 and the more ubiquitously expressed NTAL/Grb2 c... (en)
Title	Grb2 and the non-T cell activation linker NTAL constitute a Ca(2+)-regulating signal circuit in B lymphocytes Grb2 and the non-T cell activation linker NTAL constitute a Ca(2+)-regulating signal circuit in B lymphocytes (en)
skos:prefLabel	Grb2 and the non-T cell activation linker NTAL constitute a Ca(2+)-regulating signal circuit in B lymphocytes Grb2 and the non-T cell activation linker NTAL constitute a Ca(2+)-regulating signal circuit in B lymphocytes (en)
skos:notation	RIV/68378050:_____/04:00105347!RIV10-AV0-68378050
http://linked.open...avai/riv/aktivita	P Z
http://linked.open...avai/riv/aktivity	P(LN00A026), Z(AV0Z5052915)
http://linked.open...iv/cisloPeriodika	5
http://linked.open...vai/riv/dodaniDat	2010
http://linked.open...aciTvurceVysledku	Hořejší, Václav
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Ústav molekulární genetiky AV ČR, v. v. i.
http://linked.open...dnocenehoVysledku	565767
http://linked.open...ai/riv/idVysledku	RIV/68378050:_____/04:00105347
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	NTAL; Grb2; lymphocyte (en)
http://linked.open.../riv/klicoveSlovo	Grb2 lymphocyte NTAL
http://linked.open...odStatuVydavatele	US - Spojené státy americké
http://linked.open...ontrolniKodProRIV	[069D5E4043C4]
http://linked.open...i/riv/nazevZdroje	Immunity
http://linked.open...in/vavai/riv/obor	EC
http://linked.open...ichTvurcuVysledku	1 (xsd:int)
http://linked.open...cetTvurcuVysledku	8 (xsd:int)
http://linked.open...vavai/riv/projekt	Center of molecular and cellular immunology
http://linked.open...UplatneniVysledku	2004
http://linked.open...v/svazekPeriodika	21
http://linked.open...iv/tvurceVysledku	Hořejší, Václav Frey, J. Schraven, B. Wienands, J. Engelke, M. Hamm-Baarke, A. Kurosaki, T. Stork, B.
http://linked.open...n/vavai/riv/zamer	Regulace a signální cesty uplatňující se v genové expresi, imunitě, onkogenezi, replikaci virů, tvorbě buněčných struktur, chování buněk, vývoji a oplození
issn	1074-7613
number of pages	10 (xsd:int)

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