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BMC Research Notes

, 1:81

First Online: 17 September 2008Received: 22 May 2008Accepted: 17 September 2008DOI: 10.1186-1756-0500-1-81

Cite this article as: Kumar, D., Dua, R., Srikanth, R. et al. BMC Res Notes 2008 1: 81. doi:10.1186-1756-0500-1-81

Abstract

BackgroundAlthough reciprocal regulation of protein phosphorylation represents a key aspect of signal transduction, a larger perspective on how these various interactions integrate to contribute towards signal processing is presently unclear. For example, a key unanswered question is that of how phosphatase-mediated regulation of phosphorylation at the individual nodes of the signaling network translates into modulation of the net signal output and, thereby, the cellular phenotypic response.

ResultsTo address the above question we, in the present study, examined the dynamics of signaling from the B cell antigen receptor BCR under conditions where individual cellular phosphatases were selectively depleted by siRNA. Results from such experiments revealed a highly enmeshed structure for the signaling network where each signaling node was linked to multiple phosphatases on the one hand, and each phosphatase to several nodes on the other. This resulted in a configuration where individual signaling intermediates could be influenced by a spectrum of regulatory phosphatases, but with the composition of the spectrum differing from one intermediate to another. Consequently, each node differentially experienced perturbations in phosphatase activity, yielding a unique fingerprint of nodal signals characteristic to that perturbation. This heterogeneity in nodal experiences, to a given perturbation, led to combinatorial manipulation of the corresponding signaling axes for the downstream transcription factors.

ConclusionOur cumulative results reveal that it is the tight integration of phosphatases into the signaling network that provides the plasticity by which perturbation-specific information can be transmitted in the form of a multivariate output to the downstream transcription factor network. This output in turn specifies a context-defined response, when translated into the resulting gene expression profile.

AbbreviationsBCRB Cell Receptor

siRNAsmall interfering RNA

anti IgGFab2 fragment of Goat anti Mouse IgG

TFTranscription Factor

PLSPartial Least Square

PCPrinciple component

VIPVariables in Importance of Projection

Electronic supplementary materialThe online version of this article doi:10.1186-1756-0500-1-81 contains supplementary material, which is available to authorized users.

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Autor: Dhiraj Kumar - Raina Dua - Ravichandran Srikanth - Shilpi Jayaswal - Zaved Siddiqui - Kanury VS Rao

Fuente: https://link.springer.com/







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