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Publication : The strength of receptor signaling is centrally controlled through a cooperative loop between Ca2+ and an oxidant signal.

First Author  Singh DK Year  2005
Journal  Cell Volume  121
Issue  2 Pages  281-93
PubMed ID  15851034 Mgi Jnum  J:98960
Mgi Id  MGI:3580775 Doi  10.1016/j.cell.2005.02.036
Citation  Singh DK, et al. (2005) The strength of receptor signaling is centrally controlled through a cooperative loop between Ca2+ and an oxidant signal. Cell 121(2):281-93
abstractText  Activation of cell-surface receptors stimulates generation of intracellular signals that, in turn, direct the cellular response. However, mechanisms that ensure combinatorial control of these signaling events are not well understood. We show here that the Ca2+ and reactive oxygen intermediates generated upon BCR activation rapidly engage in a cooperative interaction that acts in a feedback manner to amplify the early signal generated. This cooperativity acts by regulating the concentration of the oxidant produced. The latter exerts its influence through a pulsed inactivation of receptor-coupled phosphatases, where the amplitude of this pulse is determined by oxidant concentration. The extent of phosphatase inhibition, in turn, dictates what proportion of receptor-proximal kinases are activated and, as a result, the net strength of the initial signal. It is the strength of this initial signal that finally determines the eventual duration of BCR signaling and the rate of its transmission through downstream pathways.
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