title: Advances in understanding postreceptor signaling in response to granulocyte colony-stimulating factor.
abstract: Granulocyte colony-stimulating factor (G-CSF) exerts its biologic effects through binding to its receptor expressed on myeloid cells. Like other cytokines, G-CSF induces intracellular protein tyrosine phosphorylation and activates various signaling cascades. Activation of JAK tyrosine kinases and signal transducers and activators of transcription (STAT) proteins as well as activation of the ras-MAP kinase route results in induction of gene transcription. Distinct regions or defined tyrosine residues of the G-CSF receptor cytoplasmic domain are required for complex formation with specific signaling molecules and ultimately regulate proliferation and maturation of myeloid cells. In vivo, administration of G-CSF results in increased numbers of neutrophils in normal individuals, in patients with chemotherapy-induced neutropenia, and in patients with chronic neutropenia. A subgroup of patients with severe congenital neutropenia displayed point mutations in the cytoplasmic region of the G-CSF receptor: These G-CSF receptor mutations might be involved in leukemogenesis in congenital neutropenia.
authors.affiliation: Hannover Medical School, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Tidow
authors.forename: K
authors.initials: K
authors.lastname: Welte
mesh_terms: D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology*; D006801:Humans; D009154:Mutation; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor