Tidow N, Welte K
Hannover Medical School, Germany.
Curr Opin Hematol. 1997 May;4(3):171-5. doi: 10.1097/00062752-199704030-00003.
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.
粒细胞集落刺激因子（G-CSF）通过与髓系细胞上表达的受体结合发挥其生物学效应。与其他细胞因子一样，G-CSF诱导细胞内蛋白酪氨酸磷酸化并激活各种信号级联反应。JAK酪氨酸激酶、信号转导子和转录激活子（STAT）蛋白的激活以及ras-MAP激酶途径的激活导致基因转录的诱导。G-CSF受体胞质结构域的不同区域或特定酪氨酸残基对于与特定信号分子形成复合物是必需的，并最终调节髓系细胞的增殖和成熟。在体内，给予G-CSF可使正常个体、化疗诱导的中性粒细胞减少症患者和慢性中性粒细胞减少症患者的中性粒细胞数量增加。一组严重先天性中性粒细胞减少症患者在G-CSF受体的胞质区域出现点突变：这些G-CSF受体突变可能与先天性中性粒细胞减少症的白血病发生有关。
