. "Stork, B." . "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..." . . "RIV/68378050:_____/04:00105347!RIV10-AV0-68378050" . "Frey, J." . "Schraven, B." . "Hamm-Baarke, A." . . "P(LN00A026), Z(AV0Z5052915)" . . "RIV/68378050:_____/04:00105347" . "10"^^ . . . "Grb2 and the non-T cell activation linker NTAL constitute a Ca(2+)-regulating signal circuit in B lymphocytes"@en . "NTAL; Grb2; lymphocyte"@en . . . "Ho\u0159ej\u0161\u00ED, V\u00E1clav" . . "Immunity" . . "Grb2 and the non-T cell activation linker NTAL constitute a Ca(2+)-regulating signal circuit in B lymphocytes" . "Engelke, M." . . "8"^^ . "1074-7613" . . "US - Spojen\u00E9 st\u00E1ty americk\u00E9" . "21" . "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 . "Wienands, J." . "565767" . "Kurosaki, T." . . "[069D5E4043C4]" . "1"^^ . . "Grb2 and the non-T cell activation linker NTAL constitute a Ca(2+)-regulating signal circuit in B lymphocytes"@en . . . . "Grb2 and the non-T cell activation linker NTAL constitute a Ca(2+)-regulating signal circuit in B lymphocytes" . "5" .