Open Access
Scratching the surface: signaling and routing dynamics of the CSF3 receptor
Karishma Palande1,Annemarie Meenhuis1,Tanja Jevdjovic1,Ivo P. Touw1,*
Department of Hematology, Erasmus University Medical Center, Rotterdam, Dr Molewaterplein 50, 3015 GE, The Netherlands
DOI: 10.2741/4089 Volume 18 Issue 1, pp.91-105
Published: 01 January 2013
(This article belongs to the Special Issue Regulation of signalling in health and disease)
*Corresponding Author(s):  
Ivo P. Touw

Following activation by their cognate ligands, cytokine receptors undergo intracellular routing towards lysosomes where they are degraded. Cytokine receptor signaling does not terminate at the plasma membrane, but continues throughout the endocytotic pathway. The modes of internalization and intracellular trafficking of specific receptors, the level of recycling towards the plasma membrane, the type of protein modifications (phosphorylation, ubiquitination) and the enzymes involved in these processes are remarkably diverse. This heterogeneity may contribute to the fine-tuning of signal amplitudes and duration from different receptors. The colony-stimulating factor 3 receptor (CSF3R) is unique for its balanced signaling output, first leading to proliferation of myeloid progenitors, followed by a cell cycle arrest and granulocytic differentiation. The mechanisms associated with CSF3R signal modulation, involving receptor lysine ubiquitination and redox-controlled phosphatase activities, are to a large extent confined to the signaling endosome. Interactions between signaling endosomes and the endoplasmic reticulum play a key role in this process. Here, we review the mechanisms of intracellular routing of CSF3R, their consequences for myeloid blood cell development and their implications for myeloid diseases.

Key words

CSF3 receptor, Signal transduction, JAK/STAT signaling, Intracellular trafficking, Suppressor of cytokine signaling, Deubiquitinating enzymes, Peroxiredoxin, Signaling endosome, Protein tyrosine phosphatase 1b, Review

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Karishma Palande, Annemarie Meenhuis, Tanja Jevdjovic, Ivo P. Touw. Scratching the surface: signaling and routing dynamics of the CSF3 receptor. Frontiers in Bioscience-Landmark. 2013. 18(1); 91-105.