Abstract
Following activation by their cognate ligands, cytokine receptors undergo intracellular routing toward lysosomes, where they are degraded. This review focuses on the signaling function of the G-CSFR in relation to the dynamics of endosomal routing of the G-CSFR. Mechanisms involving receptor lysine ubiquitination and redox-controlled phosphatase activities are discussed. Specific attention is paid to the consequences of G-CSFR mutations, acquired in patients with severe congenital neutropenias who receive G-CSF therapy, particularly in the context of leukemic transformation, a major clinical complication of the disease.
Copyright © 2013 Elsevier Inc. All rights reserved.
MeSH terms
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Animals
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Cell Transformation, Neoplastic / metabolism
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Congenital Bone Marrow Failure Syndromes
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Disease Progression
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Granulocyte Colony-Stimulating Factor / metabolism
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Granulocyte Colony-Stimulating Factor / therapeutic use
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Humans
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Leukemia / etiology
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Lysosomes / metabolism
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Mutation
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Neutropenia / congenital*
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Neutropenia / drug therapy
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Neutropenia / genetics
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Neutropenia / metabolism
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Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
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Reactive Oxygen Species / metabolism
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Receptors, Granulocyte Colony-Stimulating Factor / deficiency
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Receptors, Granulocyte Colony-Stimulating Factor / genetics
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Receptors, Granulocyte Colony-Stimulating Factor / metabolism*
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Signal Transduction*
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Ubiquitination
Substances
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Reactive Oxygen Species
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Receptors, Granulocyte Colony-Stimulating Factor
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Granulocyte Colony-Stimulating Factor
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PTPN1 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 1
Supplementary concepts
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Neutropenia, Severe Congenital, Autosomal Recessive 3