| Reference : Suppressor of cytokine signaling-3 is recruited to the activated granulocyte-colony s... |
| Scientific journals : Article | |||
| Life sciences : Biochemistry, biophysics & molecular biology | |||
| http://hdl.handle.net/10993/750 | |||
| Suppressor of cytokine signaling-3 is recruited to the activated granulocyte-colony stimulating factor receptor and modulates its signal transduction. | |
| English | |
| Hortner, Michael [> >] | |
| Nielsch, Ulrich [> >] | |
| Mayr, Lorenz M. [> >] | |
| Johnston, James A. [> >] | |
| Heinrich, Peter C. [> >] | |
Haan, Serge  [Rheinisch - Westfälische Technische Hochschule Aachen - RWTH > Institute for Biochemistry] | |
| 2002 | |
| Journal of immunology | |
| 169 | |
| 3 | |
| 1219-27 | |
| Yes (verified by ORBilu) | |
| International | |
| 0022-1767 | |
| United States | |
| [en] Carrier Proteins/physiology ; Cells, Cultured ; Granulocyte Colony-Stimulating Factor/pharmacology ; Humans ; Intracellular Signaling Peptides and Proteins ; Monocytes/physiology ; Neutrophils/physiology ; Proteins/physiology ; Receptors, Granulocyte Colony-Stimulating Factor/physiology ; Repressor Proteins ; Signal Transduction/physiology ; Suppressor of Cytokine Signaling Proteins ; Transcription Factors ; Tyrosine/metabolism | |
| [en] G-CSF is a polypeptide growth factor used in treatment following chemotherapy. G-CSF regulates granulopoiesis and acts on its target cells by inducing homodimerization of the G-CSFR, thereby activating intracellular signaling cascades. The G-CSFR encompasses four tyrosine motifs on its cytoplasmic tail that have been shown to recruit a number of regulatory proteins. Suppressor of cytokine signaling 3 (SOCS-3), also referred to as cytokine-inducible Src homolgy 2-containing protein 3, is a member of a recently discovered family of feedback inhibitors that have been shown to inhibit the Janus kinase/STAT pathway. In this study, we demonstrate that human SOCS-3 is rapidly induced by G-CSF in polymorphonuclear neutrophils as well as in the myeloid precursor cell line U937 and that SOCS-3 negatively regulates G-CSFR-mediated STAT activation. Most importantly, we show that SOCS-3 is recruited to the G-CSFR in a phosphorylation-dependent manner and we identify phosphotyrosine (pY)729 as the major recruitment site for SOCS-3. Furthermore, we demonstrate that SOCS-3 directly binds to this pY motif. Surface plasmon resonance analysis reveals a dissociation constant (K(D)) for this interaction of around 2.8 microM. These findings strongly suggest that the recruitment of SOCS-3 to pY729 is important for the modulation of G-CSFR-mediated signal transduction by SOCS-3. | |
| http://hdl.handle.net/10993/750 |
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