Enhanced biological effects of Phe140Asn, a novel human granulocyte colony-stimulating factor mutant, on HL60 cells.
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.
Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Suwon, Korea.
Hee Kyoung
HK
Chung
Sung Woo
SW
Kim
Sung June
SJ
Byun
Eun Mi
EM
Ko
Hak-Jae
HJ
Chung
Jae-Seok
JS
Woo
Jae Gyu
JG
Yoo
Hwi-Cheul
HC
Lee
Byoung-Chul
BC
Yang
Moosik
M
Kwon
Soo-Bong
SB
Park
Jin-Ki
JK
Park
Kyung-Woon
KW
Kim
D002454:Cell Differentiation / Q000187:drug effects; D002630:Chemotactic Factors / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology* / Q000627:therapeutic use; D018922:HL-60 Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D009154:Mutation; D009503:Neutropenia / Q000188:drug therapy; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077022:Survivin
C107489:BIRC5 protein, human; D002630:Chemotactic Factors; D051034:Inhibitor of Apoptosis Proteins; D050796:STAT3 Transcription Factor; D000077022:Survivin; D016179:Granulocyte Colony-Stimulating Factor; C507924:JAK2 protein, human; D053614:Janus Kinase 2