PMID- 10329697
OWN - NLM
STAT- MEDLINE
DCOM- 19990709
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 21
DP  - 1999 May 21
TI  - Multiple signals mediate proliferation, differentiation, and survival from the
      granulocyte colony-stimulating factor receptor in myeloid 32D cells.
PG  - 14956-62
AB  - Granulocyte colony-stimulating factor (G-CSF) regulates neutrophil production
      through activation of its cognate receptor, the G-CSF-R. Previous studies with
      deletion mutants have shown that the membrane-proximal cytoplasmic domain of the 
      receptor is sufficient for mitogenic signaling, whereas the membrane-distal
      domain is required for differentiation signaling. However, the function of the
      four cytoplasmic tyrosines of the G-CSF-R in the control of proliferation,
      differentiation, and survival has remained unclear. Here we investigated the role
      of these tyrosines by expressing a tyrosine "null" mutant and single tyrosine
      "add back" mutants in maturation-competent myeloid 32D cells. Clones expressing
      the null mutant showed only minimal proliferation and differentiation, with
      survival also reduced at low G-CSF concentrations. Analysis of clones expressing 
      the add-back mutants revealed that multiple tyrosines contribute to
      proliferation, differentiation, and survival signals from the G-CSF-R. Analysis
      of signaling pathways downstream of these tyrosines suggested a positive role for
      STAT3 activation in both differentiation and survival signaling, whereas SHP-2,
      Grb2 and Shc appear important for proliferation signaling. In addition, we show
      that a tyrosine-independent "differentiation domain" in the membrane-distal
      region of the G-CSF-R appears necessary but not sufficient for mediating
      neutrophilic differentiation in these cells.
FAU - Ward, A C
AU  - Ward AC
AD  - Institute of Hematology, Erasmus University, 3000 DR Rotterdam, The Netherlands. 
      ward@hema.fgg.eur.nl
FAU - Smith, L
AU  - Smith L
FAU - de Koning, J P
AU  - de Koning JP
FAU - van Aesch, Y
AU  - van Aesch Y
FAU - Touw, I P
AU  - Touw IP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Receptors, Granulocyte Colony-Stimulating Factor)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cell Division
MH  - Cell Survival
MH  - Leukemia, Myeloid/pathology
MH  - Mice
MH  - Mutation
MH  - Receptors, Granulocyte Colony-Stimulating Factor/*physiology
MH  - Tumor Cells, Cultured
EDAT- 1999/05/18 00:00
MHDA- 1999/05/18 00:01
CRDT- 1999/05/18 00:00
PHST- 1999/05/18 00:00 [pubmed]
PHST- 1999/05/18 00:01 [medline]
PHST- 1999/05/18 00:00 [entrez]
AID - 10.1074/jbc.274.21.14956 [doi]
AID - S0021-9258(19)73178-0 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 May 21;274(21):14956-62. doi: 10.1074/jbc.274.21.14956.