G-CSF is the most important growth factor involved in the production of neutrophilic granulocytes. Signaling routes activated upon ligand binding to the G-CSF receptor (G-CSF-R) control survival, proliferation and differentiation of myeloid progenitor cells towards mature neutrophils. Elucidation of the signaling pathways involved in this process is important for understanding normal neutrophil development and for better insights in diseases with perturbed neutrophil production such as neutropenia and myeloid leukemia. In Chapter 1 of this thesis an overview of the current knowledge on the G-CSF-R is given and the signaling pathways activated by G-CSF are introduced. Upon GCSF binding, kinases of the JAK and Src kinase families become active and the four tyrosines of the receptor, located at positions 704, 729, 744 and 764 are phosphorylated. Multiple signaling pathways are subsequently activated via recruitment of intermediates to these phosphorylated tyrosines as well as via tyrosine independent mechanisms. A well known signaling route activated by the G-CSF-R is the JAK-STAT pathway. The most prominent STATs that are activated by G-CSF are STAT3, implicated in mediating a cell cycle arrest, and STAT5, which contributes to proliferation and cell survival.

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I.P. Touw (Ivo) , B. Löwenberg (Bob)
Erasmus University Rotterdam
Löwenberg, Prof. Dr. B. (promotor), Touw, Prof. Dr. I.P. (promotor)
Erasmus MC: University Medical Center Rotterdam

van de Geijn, G.J.M. (2004, June 24). Suppressors Of Cytokine Signaling in G-CSF-induced neutrophil development. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/7402