Granulocyte colony-stimulating factor receptor signaling: implications for G-CSF responses and leukemic progression in severe congenital neutropenia.
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.
Department of Hematology, Erasmus University Medical Center, Dr Molewaterplein 50 3015 GE, Rotterdam, The Netherlands. i.touw@erasmusmc.nl
Ivo P
IP
Touw
Karishma
K
Palande
Renée
R
Beekman
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D000080984:Congenital Bone Marrow Failure Syndromes; D018450:Disease Progression; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D007938:Leukemia / Q000209:etiology; D008247:Lysosomes / Q000378:metabolism; D009154:Mutation; D009503:Neutropenia / Q000151:congenital* / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D054875:Ubiquitination
D017382:Reactive Oxygen Species; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1