| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;
Division of Cytokine Biology, Center for Biologics, Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892;
Laboratory of Biochemistry and Metabolism, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892; and
§
Institute of Hematology, Erasmus University, Rotterdam, The Netherlands
In a manner similar to many other cytokines, treatment of cells with granulocyte CSF (G-CSF) has been shown to induce the tyrosine phosphorylation of the STAT proteins. Activation of Stat1 and Stat5 by G-CSF requires the membrane-proximal cytoplasmic domain of the receptor, including box1 and box2, while G-CSF-stimulated tyrosine phosphorylation of Stat3 also requires a region distal to box 2. In this study, we show that although the membrane-proximal 55 amino acids of the G-CSF receptor are sufficient for activation of Stat5, the maximal rate of Stat5 activation requires an additional 30 amino acids of the cytoplasmic domain. In contrast, the distal carboxyl-terminal region of the receptor appears to down-regulate Stat5 activation in that deletion of this carboxyl terminus results in increased amplitude and prolonged duration of Stat5 activation by G-CSF. Significantly, expression of a truncated dominant-negative Stat5 protein in hemopoietic cells not only inhibits G-CSF-dependent cell proliferation, but also suppresses cell survival upon G-CSF withdrawal. We further show that a potential protein tyrosine phosphatase may play a critical role in the down-regulation of G-CSF-stimulated Stat5 activation. These results demonstrate that two distinct cytoplasmic regions of the G-CSF receptor are involved in the regulation of the intensity and duration of Stat5 activation, and that Stat5 may be an important player in G-CSF-mediated cell proliferation and survival.
This article has been cited by other articles:
|
|
 |
|
  X. Huang, H. Sakamoto, and M. Ogawa Thrombopoietin controls proliferation of embryonic multipotent hematopoietic progenitors Genes Cells, July 1, 2009; 14(7): 851 - 860. [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]
|
|
|
|
 |
|
 D. Zhuang, Y. Qiu, S. C. Kogan, and F. Dong Increased CCAAT Enhancer-binding Protein {epsilon} (C/EBP{epsilon}) Expression and Premature Apoptosis in Myeloid Cells Expressing Gfi-1 N382S Mutant Associated with Severe Congenital Neutropenia J. Biol. Chem., April 21, 2006; 281(16): 10745 - 10751. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Zhuang, Y. Qiu, S. J. Haque, and F. Dong Tyrosine 729 of the G-CSF receptor controls the duration of receptor signaling: involvement of SOCS3 and SOCS1 J. Leukoc. Biol., October 1, 2005; 78(4): 1008 - 1015. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. J. Stevenson, S. Haan, A. E. McClurg, M. J. McGrattan, M. A. Armstrong, P. C. Heinrich, and J. A. Johnston The Chemoattractants, IL-8 and Formyl-Methionyl-Leucyl-Phenylalanine, Regulate Granulocyte Colony-Stimulating Factor Signaling by Inducing Suppressor of Cytokine Signaling-1 Expression J. Immunol., September 1, 2004; 173(5): 3243 - 3249. [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]
|
|
|
|
|
|
K. Kusano, S. Ebara, K. Tachibana, T. Nishimura, S. Sato, T. Kuwaki, and T. Taniyama A potential therapeutic role for small nonpeptidyl compounds that mimic human granulocyte colony-stimulating factor Blood, February 1, 2004; 103(3): 836 - 842. [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]
|
|
|
|
|
|
A. Franzke, W. Piao, J. Lauber, P. Gatzlaff, C. Konecke, W. Hansen, A. Schmitt-Thomsen, B. Hertenstein, J. Buer, and A. Ganser G-CSF as immune regulator in T cells expressing the G-CSF receptor: implications for transplantation and autoimmune diseases Blood, July 15, 2003; 102(2): 734 - 739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Santini, B. Scappini, Z. K. Indik, A. Gozzini, P. Rossi Ferrini, and A. D. Schreiber The carboxy-terminal region of the granulocyte colony-stimulating factor receptor transduces a phagocytic signal Blood, June 1, 2003; 101(11): 4615 - 4622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Mitsui, S. Watanabe, Y. Taniguchi, S. Hanada, Y. Ebihara, T. Sato, T. Heike, M. Mitsuyama, T. Nakahata, and K. Tsuji Impaired neutrophil maturation in truncated murine G-CSF receptor-transgenic mice Blood, April 15, 2003; 101(8): 2990 - 2995. [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]
|
|
|
|
|
|
M. Hortner, U. Nielsch, L. M. Mayr, J. A. Johnston, P. C. Heinrich, and S. Haan Suppressor of Cytokine Signaling-3 Is Recruited to the Activated Granulocyte-Colony Stimulating Factor Receptor and Modulates its Signal Transduction J. Immunol., August 1, 2002; 169(3): 1219 - 1227. [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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
