TY - JOUR
T1 - STAT-3 activation is required for normal G-CSF-dependent proliferation and granulocytic differentiation
AU - McLemore, Morgan L.
AU - Grewal, Satkiran
AU - Liu, Fulu
AU - Archambault, Angela
AU - Poursine-Laurent, Jennifer
AU - Haug, Jeff
AU - Link, Daniel C.
N1 - Funding Information:
The authors thank Tim Graubert, Jessica Pollock, Tim Ley, and Christine Pham for their thoughtful discussions and advice. This work was supported by the Edward Mallinckrodt, Jr., Foundation (DCL), by a grant from the National Institutes of Health NHLBI (R01 HL60772-01A1 [D. C. L.]), and by a training grant from the National Institutes of Health NHLBI (T32 HL 07088-23 [M. L. M.]).
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0035102228&partnerID=8YFLogxK
U2 - 10.1016/S1074-7613(01)00101-7
DO - 10.1016/S1074-7613(01)00101-7
M3 - Article
C2 - 11239451
AN - SCOPUS:0035102228
SN - 1074-7613
VL - 14
SP - 193
EP - 204
JO - Immunity
JF - Immunity
IS - 2
ER -