STAT-3 activation is required for normal G-CSF-dependent proliferation and granulocytic differentiation.

摘要: To investigate the role of signal transducer and activator transcription (STAT) proteins in granulocyte colony-stimulating factor (G-CSF)-regulated biological responses, we generated transgenic mice with a targeted mutation their G-CSF receptor (termed d715F) that abolishes G-CSF-dependent STAT-3 activation attenuates STAT-5 activation. Homozygous mutant are severely neutropenic an accumulation immature myeloid precursors bone marrow. G-CSF-induced proliferation granulocytic differentiation hematopoietic progenitors is impaired. Expression constitutively active form d715F nearly completely rescued these defects. Conversely, expression dominant-negative wild-type results impaired differentiation. These data suggest by G-CSFR critical for transduction normal proliferative signals contributes to differentiative signals.