Signal transduction pathways of GM-CSF in neural cell lines.
GM-CSF is recently being suggested to play important role(s) in the nervous system. Present study was intended to understand signal transduction pathways of GM-CSF in human neuroblastoma (SK-N-(BE)2) and glioblastoma (A172) cell lines. The expression of GM-CSF receptors on the surface of these cells was confirmed by immunocytochemistry, Western blot analysis and RT-PCR. When treated for 10min, GM-CSF activated the signal transducer and activator of transcription 5 (STAT5) and extracellular signal regulated kinase (ERK) in both cell lines. However, Janus kinase 2 (JAK2) was activated only in A172 cells but not in SK-N-(BE)2 cells by GM-CSF. The GM-CSF-activated cellular signal pathways were specifically inhibited by the pretreatment of GM-CSF receptor alpha antibody, suggesting the specificity of the signal activation. The experiment using specific inhibitors (AG490) to the JAK/STAT pathway showed that JAK2/STAT5 cascade was well preserved and activated by GM-CSF in A172 cells, while STAT5 was activated by GM-CSF without JAK2 activation in SK-N-(EB)2 cells. The ERK pathway was activated by GM-CSF independently of JAK2 in both cell lines. Finally, GM-CSF showed cytoprotective effect on these cell lines by inhibiting cytotoxicity of saturosporine. The results revealed the signal transduction pathways activated by GM-CSF in neural cells and suggested that GM-CSF might affect the neural functions via these signal pathways.
Choi
Jung Kyoung
JK
Inha Neural Repair Center, Inha University Hospital, Inha University College of Medicine, Incheon, Republic of Korea.
Choi
Byung Hyune
BH
Ha
Yoon
Y
Park
Hyeonseon
H
Yoon
Seung Hwan
SH
Park
Hyung Chun
HC
Park
So Ra
SR
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D011247:Pregnancy; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D013234:Stem Cells / Q000502:physiology
D004791:Enzyme Inhibitors; D050799:STAT5 Transcription Factor; D012313:RNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007770:L-Lactate Dehydrogenase; D053614:Janus Kinase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D019311:Staurosporine