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

Singh, Dinesh Kumar ; Kumar, Dhiraj ; Siddiqui, Zaved ; Basu, Sandip Kumar ; Kumar, Vikas ; Rao, Kanury V. S. (2005) The strength of receptor signaling is centrally controlled through a cooperative loop between Ca2+ and an oxidant signal Cell, 121 (2). pp. 281-293. ISSN 0092-8674

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Official URL: http://www.cell.com/retrieve/pii/S0092867405001534

Related URL: http://dx.doi.org/10.1016/j.cell.2005.02.036

Abstract

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.

Item Type:Article
Source:Copyright of this article belongs to Cell Press Inc.
ID Code:1798
Deposited On:08 Oct 2010 12:29
Last Modified:16 May 2016 12:51

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