Signal transduction of granulocyte macrophage-colony stimulating factor in a human endothelium-derived cell line.
Granulocyte macrophage-colony stimulating factor (GM-CSF) regulates the growth and differentiation of hematopoietic cells and is also involved in angiogenesis. The induction of protein tyrosine phosphorylation is critical for cytokines and growth factor-mediated signal transduction. The protein tyrosine kinase (PTK), JAK2 is involved in signaling through a number of cytokine receptors, including GM-CSF receptors. In the present study, we investigated the effect of GM-CSF on the cell cycle and protein tyrosine phosphorylation in a human endothelial cell-derived cell line, EA.hy 926 cells. GM-CSF induced the cell cycle progression and tyrosine phosphorylation of cellular proteins including JAK2 kinase in EA.hy 926 cells. Herbimycin A, a PTK inhibitor, completely blocked the GM-CSF-induced cell cycle progression, protein tyrosine phosphorylation and JAK2 kinase activation in EA.hy 926 cells. Our results demonstrate that protein tyrosine phosphorylation and JAK2 kinase activation are closely related to the GM-CSF-mediated signal transduction and growth in vascular endothelial cells, and suggest the efficacy of herbimycin A in controlling angiogenesis.
Tsukada
T
T
The First Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Japan.
Eguchi
K
K
Migita
K
K
Kawabe
Y
Y
Nagataki
S
S
D016227:Benzoquinones; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D053614:Janus Kinase 2; D047029:Lactams, Macrocyclic; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011518:Proto-Oncogene Proteins; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism; D014471:Umbilical Veins
D016227:Benzoquinones; D006131:Growth Inhibitors; D047029:Lactams, Macrocyclic; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D011809:Quinones; D017828:Rifabutin; D014443:Tyrosine; C020754:herbimycin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2