Investigating the Effects of SFK and Mek Inhibitors on G-CSF Signaling

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Granulocyte-Colony Stimulating Factor (G-CSF) is known as a growth factor that positively regulates neutrophil development. G-CSF supports neutrophil differentiation by binding to the G-CSF Receptor (G-CSFR), leading to the activation of downstream signaling pathways such as the Jak/Stat, Mek/Erk1/2 and Src-Family Kinases (SFKs). However, the molecular mechanisms by which G-CSF acts in myeloid development remain incompletely understood. The SFKs have been shown to play a critical role in monocyte development, but significantly less is known about their roles in neutrophil development. The Dong lab recently showed that tyrosine (Y) 729 in the cytoplasmic domain of G-CSFR controls neutrophil versus monocyte development of myeloid precursors by regulating Mek/Erk1/2 pathway and downstream transcription factors c-Fos/Egr-1. As the SFKs have been shown to activate Mek/Erk1/2 signaling pathway, we examined whether they are involved in the regulation of neutrophil development in response to G-CSF. We show here that SFKs appeared to regulate the different aspects of neutrophil versus monocyte development. Additional studies are needed to further clarify the roles of SFKs in myeloid development.

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