TAILIEUCHUNG - Báo cáo Y học: Acceleration of granulocyte colony-stimulating factor-induced neutrophilic nuclear lobulation by overexpression of Lyn tyrosine kinase

Stimulation with granulocyte colony-stimulating factor (G-CSF) induces myeloid precursor cells to di erentiate into neutrophils, and tyrosine phosphorylation of certain cellular proteins is crucial to this process. However, the signaling pathways for neutrophil di erentiation are still obscure. As the Src-like tyrosine kinase, Lyn, has been reported to play a role in G-CSF-induced proliferation in avian lymphoid cells, we examined its involvement in G-CSF-induced signal transduction in mammalian cells | Eur. J. Biochem. 269 381-389 2002 FEBS 2002 Acceleration of granulocyte colony-stimulating factor-induced neutrophilic nuclear lobulation by overexpression of Lyn tyrosine kinase Tomomi Omura Hiroshi Sakai and Hiroshi Murakami1 Department of Biotechnology Faculty of Engineering Okayama University Japan Stimulation with granulocyte colony-stimulating factor G-CSF induces myeloid precursor cells to differentiate into neutrophils and tyrosine phosphorylation of certain cellular proteins is crucial to this process. However the signaling pathways for neutrophil differentiation are still obscure. As the Src-like tyrosine kinase Lyn has been reported to play a role in G-CSF-induced proliferation in avian lymphoid cells we examined its involvement in G-CSF-induced signal transduction in mammalian cells. Expression plasmids for wild-type Lyn Lyn and kinasenegative Lyn LynKN were introduced into a murine granulocyte precursor cell line GM-I62M that can respond to G-CSF with neutrophil differentiation and cell lines that overexpressed these molecules GM-Lyn GM-LynKN were established. Upon G-CSF stimulation both the GM-Lyn and GM-LynKN cells began to differentiate into neutrophils showing early morphological changes within a few days much more rapidly than did the parental cells which started to exhibit nuclear lobulation about 10 days after the cells were transferred to G-CSF-containing medium. However the time course of expression of the myeloperoxidase gene another neutrophil differentiation marker was not affected by the overexpression of Lyn or LynKN. Therefore in normal cells protein interactions with Lyn but not its kinase activity are important for the induction of G-CSF-induced neutrophilic nuclear lobulation in mammalian granulopoiesis. Keywords differentiation granulocyte colony-stimulating factor G-CSF granulocyte lobulation neutrophil. The production of blood cells is regulated by a variety of extracellular stimuli including a network of hematopoietic growth .

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