Formation of Intracellular Concentration Landscapes by Multisite Protein Modification

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Title: Formation of Intracellular Concentration Landscapes by Multisite Protein Modification
Authors: Muñoz-García, Javier
Kholodenko, Boris N.
Neufeld, Zoltán
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Date: Jul-2010
Abstract: Multiple cellular proteins are covalently modified (e.g., phosphorylated/dephosphorylated) at several sites, which leads to diverse signaling activities. Here, we consider a signaling cascade that is activated at the plasma membrane and composed of two-site protein modification cycles, and we focus on the radial profile of the concentration landscapes created by different protein forms in the cytoplasm. We show that under proper conditions, the concentrations of modified proteins generate a series of peaks that propagate into the cell interior. Proteins modified at both sites form activity gradients with long plateaus that abruptly decay at successive locations along the path from the membrane to the nucleus. We demonstrate under what conditions signals generated at the membrane stall in the vicinity of that membrane or propagate into the cell. We derive analytical approximations for the main characteristics of the protein concentration profiles and demonstrate what we believe to be a novel steady-state pattern formation mechanism capable of generating precise spatial guidance for diverse cellular processes.
Type of material: Journal Article
Publisher: Elsevier
Journal: Biophysical Journal
Volume: 99
Issue: 1
Start page: 59
End page: 66
Copyright (published version): 2010 Elsevier
Keywords: intracellular concentration landscapesmultisite protein modificationprotein concentration profiles
DOI: 10.1016/j.bpj.2010.04.014
Language: en
Status of Item: Peer reviewed
Appears in Collections:SBI Research Collection

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