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

Morgan L. McLemore, Satkiran Grewal, Fulu Liu, Angela Archambault, Jennifer Poursine-Laurent, Jeff Haug, Daniel C. Link

Research output: Contribution to journalArticlepeer-review

169 Scopus citations

Abstract

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

Original languageEnglish
Pages (from-to)193-204
Number of pages12
JournalImmunity
Volume14
Issue number2
DOIs
StatePublished - 2001

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