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KMID : 0624620110440100686
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BMB Reports
2011 Volume.44 No. 10 p.686 ~ p.691
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Enhanced biological effects of Phe140Asn, a novel human granulocyte colony-stimulating factor mutant, on HL60 cells
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Chung Hee-Kyoung
Kim Sung-Woo
Byun Sung-June
Ko Eun-Mi
Chung Hak-Jae
Woo Jae-Seok
Yoo Jae-Gyu
Lee Hwi-Cheul
Yang Byoung-Chul
Kwon Moo-Sik
Park Soo-Bong
Park Jin-Ki
Kim Kyung-Woon
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Abstract
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Granulocyte colony-stimulating factor (G-CSF) is a cytokine secreted by stromal cells and plays a role in the differentiation of bone marrow stem cells and proliferation of neutrophils. Therefore, G-CSF is widely used to reduce the risk of serious infection in immunocompromised patients; however, its use in such patients is limited because of its non-persistent biological activity. We created an N-linked glycosylated form of this cytokine, hG-CSF (Phe140Asn), to assess its biological activity in the promyelocyte cell line HL60. Enhanced biological effects were identified by analyzing the JAK2/STAT3/survivin pathway in HL60 cells. In addition, mutant hG-CSF (Phe140Asn) was observed to have enhanced chemoattractant effects and improved differentiation efficiency in HL60 cells. These results suggest that the addition of N-linked glycosylation was successful in improving the biological activity of hG-CSF. Furthermore, the mutated product appears to be a feasible therapy for patients with neutropenia.
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KEYWORD
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Biological activity, G-CSF, Neutropenia, N-linked glycosylation
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