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- Title
Subcellular localization of Grb2 by the adaptor protein Dok-3 restricts the intensity of Ca<sup>2+</sup> signaling in B cells.
- Authors
Stork, Björn; Neumann, Konstantin; Goldbeck, Ingo; Alers, Sebastian; Kähne, Thilo; Naumann, Michael; Engelke, Michael; Wienands, Jürgen
- Abstract
Spatial and temporal modulation of intracellular Ca2+ fluxes controls the cellular response of B lymphocytes to antigen stimulation. Herein, we identify the hematopoietic adaptor protein Dok-3 (downstream of kinase-3) as a key component of negative feedback regulation in Ca2+ signaling from the B-cell antigen receptor. Dok-3 localizes at the inner leaflet of the plasma membrane and is a major substrate for activated Src family kinase Lyn. Phosphorylated Dok-3 inhibits antigen receptor-induced Ca2+ elevation by recruiting cytosolic Grb2, which acts at this location as a negative regulator of Bruton's tyrosine kinase. This leads to diminished activation of phospholipase C-γ2 and reduced production of soluble inositol trisphosphate. Hence, the Dok-3/Grb2 module is a membrane-associated signaling organizer, which orchestrates the interaction efficiency of Ca2+-mobilizing enzymes.
- Subjects
B cells; LYMPHOCYTES; PROTEINS; CELL membranes; PROTEIN-tyrosine kinases
- Publication
EMBO Journal, 2007, Vol 26, Issue 4, p1140
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1038/sj.emboj.7601557