Document Detail

Scratching the surface: signaling and routing dynamics of the CSF3 receptor.
MedLine Citation:
PMID:  23276911     Owner:  NLM     Status:  MEDLINE    
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.
Karishma Palande; Annemarie Meenhuis; Tanja Jevdjovic; Ivo P Touw
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2013-01-01
Journal Detail:
Title:  Frontiers in bioscience (Landmark edition)     Volume:  18     ISSN:  1093-4715     ISO Abbreviation:  Front Biosci (Landmark Ed)     Publication Date:  2013  
Date Detail:
Created Date:  2013-01-01     Completed Date:  2013-06-12     Revised Date:  2013-07-29    
Medline Journal Info:
Nlm Unique ID:  101612996     Medline TA:  Front Biosci (Landmark Ed)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  91-105     Citation Subset:  IM    
Department of Hematology, Erasmus University Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
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MeSH Terms
Endocytosis / genetics
Endopeptidases / metabolism
Endosomal Sorting Complexes Required for Transport / metabolism
Janus Kinases / metabolism
Leukemia, Myeloid, Acute / physiopathology
Lysine / metabolism
Lysosomes / metabolism
Neutropenia / congenital,  physiopathology
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism
Receptors, Colony-Stimulating Factor / physiology*,  therapeutic use
Signal Transduction / physiology*
Ubiquitin Thiolesterase / metabolism
Reg. No./Substance:
0/CSF3R protein, human; 0/Endosomal Sorting Complexes Required for Transport; 0/Receptors, Colony-Stimulating Factor; 0/USP8 protein, human; 56-87-1/Lysine; EC Kinases; EC Thiolesterase; EC protein, human; EC protein, human; EC Tyrosine Phosphatase, Non-Receptor Type 1; EC Tyrosine Phosphatase, Non-Receptor Type 6; EC 3.4.-/Endopeptidases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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