|
|
Prepublished online as a Blood First Edition Paper on December 5, 2002; DOI 10.1182/blood-2002-07-2062.
 Previous Article | Table of Contents | Next Article 
Blood, 1 April 2003, Vol. 101, No. 7, pp. 2584-2590
HEMATOPOIESIS
Signaling mechanisms coupled to tyrosines in the granulocyte
colony-stimulating factor receptor orchestrate G-CSF-induced expansion
of myeloid progenitor cells
Mirjam H. A. Hermans,
Gert-Jan van de Geijn,
Claudia Antonissen,
Judith Gits,
Daphne van Leeuwen,
Alister C. Ward, and
Ivo P. Touw
From the Institute of Hematology, Erasmus University of
Rotterdam, the Netherlands; and Deakin University,
Burwood, Victoria, Australia.
Granulocyte colony-stimulating factor (G-CSF) is the
major regulator of neutrophil production. Studies in cell lines have established that conserved tyrosines Tyr704, Tyr729, Tyr744,
Tyr764 within the cytoplasmic domain of G-CSF receptor
(G-CSF-R) contribute significantly to G-CSF-induced proliferation,
differentiation, and cell survival. However, it is unclear whether
these tyrosines are equally important under more physiologic
conditions. Here, we investigated how individual G-CSF-R tyrosines
affect G-CSF responses of primary myeloid progenitors. We generated
G-CSF-R-deficient mice and transduced their bone marrow cells with
tyrosine "null" mutant (m0), single tyrosine
"add-back" mutants, or wild-type (WT) receptors. G-CSF-induced
responses were determined in primary colony assays, serial replatings,
and suspension cultures. We show that removal of all tyrosines had no
major influence on primary colony growth. However, adding back Tyr764
strongly enhanced proliferative responses, which was reverted by
inhibition of ERK activity. Tyr729, which we found to be associated
with the suppressor of cytokine signaling, SOCS3, had a negative effect
on colony formation. After repetitive replatings, the clonogenic
capacities of cells expressing m0 gradually dropped compared with WT.
The presence of Tyr729, but also Tyr704 and Tyr744, both involved in
activation of signal transducer and activator of transcription 3 (STAT3), further reduced replating efficiencies. Conversely, Tyr764
greatly elevated the clonogenic abilities of myeloid progenitors,
resulting in a more than 104-fold increase of
colony-forming cells over m0 after the fifth replating. These findings
suggest that tyrosines in the cytoplasmic domain of G-CSF-R, although
dispensable for G-CSF-induced colony growth, recruit signaling
mechanisms that regulate the maintenance and outgrowth of myeloid
progenitor cells.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
C. Liongue, C. J. Hall, B. A. O'Connell, P. Crosier, and A. C. Ward
Zebrafish granulocyte colony-stimulating factor receptor signaling promotes myelopoiesis and myeloid cell migration
Blood,
March 12, 2009;
113(11):
2535 - 2546.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Jiang, N. Hein, K. Eckert, J. Luscher-Firzlaff, and B. Luscher
Regulation of the MAD1 promoter by G-CSF
Nucleic Acids Res.,
March 1, 2008;
36(5):
1517 - 1531.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Boyle, P. Egan, S. Rakar, T. A. Willson, I. P. Wicks, D. Metcalf, D. J. Hilton, N. A. Nicola, W. S. Alexander, A. W. Roberts, et al.
The SOCS box of suppressor of cytokine signaling-3 contributes to the control of G-CSF responsiveness in vivo
Blood,
September 1, 2007;
110(5):
1466 - 1474.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. D. Emanuel
Drifting precariously due to lost tyrosines
Blood,
January 1, 2007;
109(1):
7 - 8.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Germeshausen, M. Ballmaier, and K. Welte
Incidence of CSF3R mutations in severe congenital neutropenia and relevance for leukemogenesis: results of a long-term survey
Blood,
January 1, 2007;
109(1):
93 - 99.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Wolfler, S. J. Erkeland, C. Bodner, M. Valkhof, W. Renner, C. Leitner, W. Olipitz, M. Pfeilstocker, C. Tinchon, W. Emberger, et al.
A functional single-nucleotide polymorphism of the G-CSF receptor gene predisposes individuals to high-risk myelodysplastic syndrome
Blood,
May 1, 2005;
105(9):
3731 - 3736.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kamezaki, K. Shimoda, A. Numata, T. Haro, H. Kakumitsu, M. Yoshie, M. Yamamoto, K. Takeda, T. Matsuda, S. Akira, et al.
Roles of Stat3 and ERK in G-CSF Signaling
Stem Cells,
February 1, 2005;
23(2):
252 - 263.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. G. Hunter, A. Jacob, L. C. O'Donnell, A. Agler, L. J. Druhan, K. M. Coggeshall, and B. R. Avalos
Loss of SHIP and CIS Recruitment to the Granulocyte Colony-Stimulating Factor Receptor Contribute to Hyperproliferative Responses in Severe Congenital Neutropenia/Acute Myelogenous Leukemia
J. Immunol.,
October 15, 2004;
173(8):
5036 - 5045.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G.-J. M. van de Geijn, J. Gits, L. H. J. Aarts, C. Heijmans-Antonissen, and I. P. Touw
G-CSF receptor truncations found in SCN/AML relieve SOCS3-controlled inhibition of STAT5 but leave suppression of STAT3 intact
Blood,
August 1, 2004;
104(3):
667 - 674.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G.-J. M. van de Geijn, J. Gits, and I. P. Touw
Distinct activities of suppressor of cytokine signaling (SOCS) proteins and involvement of the SOCS box in controlling G-CSF signaling
J. Leukoc. Biol.,
July 1, 2004;
76(1):
237 - 244.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q.-S. Zhu, L. J. Robinson, V. Roginskaya, and S. J. Corey
G-CSF-induced tyrosine phosphorylation of Gab2 is Lyn kinase dependent and associated with enhanced Akt and differentiative, not proliferative, responses
Blood,
May 1, 2004;
103(9):
3305 - 3312.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Okamura, N. Iwata, A. Nagata, A. Tamekane, M. Shimoyama, H. Gomyo, K. Yakushijin, N. Urahama, M. Hamaguchi, C. Fukui, et al.
Involvement of casein kinase I{epsilon} in cytokine-induced granulocytic differentiation
Blood,
April 15, 2004;
103(8):
2997 - 3004.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Kimura, I. Kinjyo, Y. Matsumura, H. Mori, R. Mashima, M. Harada, K. R. Chien, H. Yasukawa, and A. Yoshimura
SOCS3 Is a Physiological Negative Regulator for Granulopoiesis and Granulocyte Colony-stimulating Factor Receptor Signaling
J. Biol. Chem.,
February 20, 2004;
279(8):
6905 - 6910.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
