|
|
 Previous Article | Table of Contents | Next Article 
The membrane-distal cytoplasmic region of human granulocyte colony-
stimulating factor receptor is required for STAT3 but not STAT1 homodimer
formation
JP de Koning, F Dong, L Smith, AM Schelen, RM Barge, DC van der Plas, LH Hoefsloot, B Lowenberg and IP Touw
Institute of Hematology, Erasmus University, Rotterdam, The Netherlands.
Signal transduction from the granulocyte colony-stimulating factor receptor
(G-CSF-R) involves the activation of the Janus tyrosine kinase/signal
transducer and activator of transcription (Jak/STAT) pathway. G-CSF induces
tyrosine phosphorylation of Jak1, Jak2, STAT1, and STAT3. The
membrane-proximal region of G-CSF-R is sufficient for activation of Jaks.
It is still unclear how STAT proteins are activated by G-CSF-R. We
investigated the possible involvement of the C-terminal region of G-CSF-R
in the recruitment of STAT proteins using BAF3 cell transfectants
expressing wild type (WT) G-CSF-R, C-terminal deletion mutants and
tyrosine-to-phenylalanine substitution mutants. Electrophoretic mobility
shift assays with STAT-binding oligonucleotides (m67) showed that
activation of WT G-CSF-R induces three distinct STAT complexes, namely
STAT3 homodimers, STAT1-STAT3 heterodimers, and STAT1 homodimers. However,
STAT1 homodimers and STAT1- STAT3 heterodimers were predominantly formed
after activation of a C- terminal deletion mutant d685, which lacks all
four conserved cytoplasmic tyrosine residues, located at positions 704,
729, 744, and 764. Antiphosphotyrosine immunoblots of STAT3
immunoprecipitates showed that activation of WT G-CSF-R induced
phosphorylation of STAT3. In contrast, no phosphorylation of STAT3 was
observed after activation of deletion mutant d685. These findings establish
that the C-terminal region of G-CSF-R plays a major role in the activation
of STAT3. By using tyrosine-to-phenylalanine substitution mutants of
G-CSF-R, we further show that tyrosine 704, present in a YXXQ consensus
sequence shown to be essential for STAT3 binding to gp130, is not
exclusively involved in the activation of STAT3 by G-CSF-R.
Volume 87,
Issue 4,
pp. 1335-1342,
02/15/1996
Copyright © 1996 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
G. R. Romeo and A. Kazlauskas
Oxysterol and Diabetes Activate STAT3 and Control Endothelial Expression of Profilin-1 via OSBP1
J. Biol. Chem.,
April 11, 2008;
283(15):
9595 - 9605.
[Abstract]
[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]
|
|
|
|
|
|
|
E. M. Sloand, A. S. M. Yong, S. Ramkissoon, E. Solomou, T. C. Bruno, S. Kim, M. Fuhrer, S. Kajigaya, A. J. Barrett, and N. S. Young
Granulocyte colony-stimulating factor preferentially stimulates proliferation of monosomy 7 cells bearing the isoform IV receptor
PNAS,
September 26, 2006;
103(39):
14483 - 14488.
[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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
L. H. J. Aarts, O. Roovers, A. C. Ward, and I. P. Touw
Receptor activation and 2 distinct COOH-terminal motifs control G-CSF receptor distribution and internalization kinetics
Blood,
January 15, 2004;
103(2):
571 - 579.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Wiederkehr-Adam, P. Ernst, K. Muller, E. Bieck, F. O. Gombert, J. Ottl, P. Graff, F. Grossmuller, and M. H. Heim
Characterization of Phosphopeptide Motifs Specific for the Src Homology 2 Domains of Signal Transducer and Activator of Transcription 1 (STAT1) and STAT3
J. Biol. Chem.,
April 25, 2003;
278(18):
16117 - 16128.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H. A. Hermans, G.-J. van de Geijn, C. Antonissen, J. Gits, D. van Leeuwen, A. C. Ward, and I. P. Touw
Signaling mechanisms coupled to tyrosines in the granulocyte colony-stimulating factor receptor orchestrate G-CSF-induced expansion of myeloid progenitor cells
Blood,
April 1, 2003;
101(7):
2584 - 2590.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. L. Hevehan, W. M. Miller, and E. T. Papoutsakis
Differential expression and phosphorylation of distinct STAT3 proteins during granulocytic differentiation
Blood,
March 1, 2002;
99(5):
1627 - 1637.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Dong, Y. Qiu, T. Yi, I. P. Touw, and A. C. Larner
The Carboxyl Terminus of the Granulocyte Colony- Stimulating Factor Receptor, Truncated in Patients with Severe Congenital Neutropenia/Acute Myeloid Leukemia, Is Required for SH2-Containing Phosphatase-1 Suppression of Stat Activation
J. Immunol.,
December 1, 2001;
167(11):
6447 - 6452.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. White, M. H. Alarcon, and D. J. Tweardy
Inhibition of granulocyte colony-stimulating factor-mediated myeloid maturation by low level expression of the differentiation-defective class IV granulocyte colony-stimulating factor receptor isoform
Blood,
June 1, 2000;
95(11):
3335 - 3340.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-T. Tsai, Y.-H. Su, S.-S. Fang, T.-N. Huang, Y. Qiu, Y.-S. Jou, H.-m. Shih, H.-J. Kung, and R.-H. Chen
Etk, a Btk Family Tyrosine Kinase, Mediates Cellular Transformation by Linking Src to STAT3 Activation
Mol. Cell. Biol.,
March 15, 2000;
20(6):
2043 - 2054.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
F. Dong and A. C. Larner
Activation of Akt kinase by granulocyte colony-stimulating factor (G-CSF): evidence for the role of a tyrosine kinase activity distinct from the janus kinases
Blood,
March 1, 2000;
95(5):
1656 - 1662.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Ward, I. Touw, and A. Yoshimura
The Jak-Stat pathway in normal and perturbed hematopoiesis
Blood,
January 1, 2000;
95(1):
19 - 29.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kanayasu-Toyoda, T. Yamaguchi, E. Uchida, and T. Hayakawa
Commitment of Neutrophilic Differentiation and Proliferation of HL-60 Cells Coincides with Expression of Transferrin Receptor. EFFECT OF GRANULOCYTE COLONY STIMULATING FACTOR ON DIFFERENTIATION AND PROLIFERATION
J. Biol. Chem.,
September 3, 1999;
274(36):
25471 - 25480.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Ward, Y. M. van Aesch, J. Gits, A. M. Schelen, J. P. de Koning, D. van Leeuwen, M. H. Freedman, and I. P. Touw
Novel Point Mutation in the Extracellular Domain of the Granulocyte Colony-Stimulating Factor (G-Csf) Receptor in a Case of Severe Congenital Neutropenia Hyporesponsive to G-Csf Treatment
J. Exp. Med.,
August 16, 1999;
190(4):
497 - 508.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Carballo, M. Conde, R. El Bekay, J. Martin-Nieto, M. J. Camacho, J. Monteseirin, J. Conde, F. J. Bedoya, and F. Sobrino
Oxidative Stress Triggers STAT3 Tyrosine Phosphorylation and Nuclear Translocation in Human Lymphocytes
J. Biol. Chem.,
June 18, 1999;
274(25):
17580 - 17586.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. L. Ilaria Jr, R. G. Hawley, and R. A. Van Etten
Dominant Negative Mutants Implicate STAT5 in Myeloid Cell Proliferation and Neutrophil Differentiation
Blood,
June 15, 1999;
93(12):
4154 - 4166.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Yamaguchi, T. Mukasa, E. Uchida, T. Kanayasu-Toyoda, and T. Hayakawa
The Role of STAT3 in Granulocyte Colony-stimulating Factor-induced Enhancement of Neutrophilic Differentiation of Me2SO-treated HL-60 Cells. GM-CSF INHIBITS THE NUCLEAR TRANSLOCATION OF TYROSINE-PHOSPHORYLATED STAT3
J. Biol. Chem.,
May 28, 1999;
274(22):
15575 - 15581.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Ward, L. Smith, J. P. de Koning, Y. van Aesch, and I. P. Touw
Multiple Signals Mediate Proliferation, Differentiation, and Survival from the Granulocyte Colony-stimulating Factor Receptor in Myeloid 32D Cells
J. Biol. Chem.,
May 21, 1999;
274(21):
14956 - 14962.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H.A. Hermans, C. Antonissen, A. C. Ward, A. E.M. Mayen, R. E. Ploemacher, and I. P. Touw
Sustained Receptor Activation and Hyperproliferation in Response to Granulocyte Colony-stimulating Factor (G-CSF) in Mice with a Severe Congenital Neutropenia/Acute Myeloid Leukemia-derived Mutation in the G-CSF Receptor Gene
J. Exp. Med.,
February 15, 1999;
189(4):
683 - 692.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Besser, J. F. Bromberg, J. E. Darnell Jr., and H. Hanafusa
A Single Amino Acid Substitution in the v-Eyk Intracellular Domain Results in Activation of Stat3 and Enhances Cellular Transformation
Mol. Cell. Biol.,
February 1, 1999;
19(2):
1401 - 1409.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Ward, Y. M. van Aesch, A. M. Schelen, and I. P. Touw
Defective Internalization and Sustained Activation of Truncated Granulocyte Colony-Stimulating Factor Receptor Found in Severe Congenital Neutropenia/Acute Myeloid Leukemia
Blood,
January 15, 1999;
93(2):
447 - 458.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Ward, M. H.A. Hermans, L. Smith, Y. M. van Aesch, A. M. Schelen, C. Antonissen, and I. P. Touw
Tyrosine-Dependent and -Independent Mechanisms of STAT3 Activation by the Human Granulocyte Colony-Stimulating Factor (G-CSF) Receptor Are Differentially Utilized Depending on G-CSF Concentration
Blood,
January 1, 1999;
93(1):
113 - 124.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Dong, X. Liu, J. P. de Koning, I. P. Touw, L. Henninghausen, A. Larner, and P. M. Grimley
Stimulation of Stat5 by Granulocyte Colony-Stimulating Factor (G-CSF) Is Modulated by Two Distinct Cytoplasmic Regions of the G-CSF Receptor
J. Immunol.,
December 15, 1998;
161(12):
6503 - 6509.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. de Koning, A. A. Soede-Bobok, A. M. Schelen, L. Smith, D. van Leeuwen, V. Santini, B. M.T. Burgering, J. L. Bos, B. Lowenberg, and I. P. Touw
Proliferation Signaling and Activation of Shc, p21Ras, and Myc Via Tyrosine 764 of Human Granulocyte Colony-Stimulating Factor Receptor
Blood,
March 15, 1998;
91(6):
1924 - 1933.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Shimozaki, K. Nakajima, T. Hirano, and S. Nagata
Involvement of STAT3 in the Granulocyte Colony-stimulating Factor-induced Differentiation of Myeloid Cells
J. Biol. Chem.,
October 3, 1997;
272(40):
25184 - 25189.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Shimoda, J. Feng, H. Murakami, S. Nagata, D. Watling, N. C. Rogers, G. R. Stark, I. M. Kerr, and J. N. Ihle
Jak1 Plays an Essential Role for Receptor Phosphorylation and Stat Activation in Response to Granulocyte Colony-Stimulating Factor
Blood,
July 15, 1997;
90(2):
597 - 604.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Kirken, M. G. Malabarba, J. Xu, L. DaSilva, R. A. Erwin, X. Liu, L. Hennighausen, H. Rui, and W. L. Farrar
Two Discrete Regions of Interleukin-2 (IL2) Receptor beta Independently Mediate IL2 Activation of a PD98059/Rapamycin/Wortmannin-insensitive Stat5a/b Serine Kinase
J. Biol. Chem.,
June 13, 1997;
272(24):
15459 - 15465.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. H. Hoefsloot, M. P. van Amelsvoort, L. C.A.M. Broeders, D. C. van der Plas, K. van Lom, H. Hoogerbrugge, I. P. Touw, and B. Lowenberg
Erythropoietin-Induced Activation of STAT5 Is Impaired in the Myelodysplastic Syndrome
Blood,
March 1, 1997;
89(5):
1690 - 1700.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. E. Nicholson, R. Starr, U. Novak, D. J. Hilton, and J. E. Layton
Tyrosine Residues in the Granulocyte Colony-stimulating Factor (G-CSF) Receptor Mediate G-CSF-induced Differentiation of Murine Myeloid Leukemic (M1) Cells
J. Biol. Chem.,
October 25, 1996;
271(43):
26947 - 26953.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Dong, J. S. Gutkind, and A. C. Larner
Granulocyte Colony-stimulating Factor Induces Erk5 Activation, Which Is Differentially Regulated by Protein-tyrosine Kinases and Protein Kinase C. REGULATION OF CELL PROLIFERATION AND SURVIVAL
J. Biol. Chem.,
March 30, 2001;
276(14):
10811 - 10816.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
