Granulocyte-macrophage colony stimulating factor stimulates rapid phosphorylation of proteins on tyrosines in human U937 and HL-60 leukemic cells.
GM-CSF is a colony stimulating factor which regulates growth and differentiation of hematopoietic progenitors. Also, it stimulates increases in c-jun expression and activates AP-1 enhancer activity. However, it is not clearly known how its signal is transduced. In this study, the effect of GM-CSF on tyrosyl phosphorylation was examined in Human U937 and HL-60 Leukemic cells by Western Blotting using anti-phosphotyrosine monoclonal antibody and autoradiography. Evidence is presented that GM-CSF stimulates a rapid phosphorylation on tyrosines of several proteins of relative Mr. 150, 110, 95, 55, 48, and 15 kDa within 60 seconds. The effect of GM-CSF was blocked by the tyrosine kinase inhibitor ST638 but not by H-7. Both G-CSF and M-CSF were also effective in stimulating tyrosine phosphorylation. These results strongly support a role for tyrosine kinases in regulation of cellular events by GM-CSF in monoblasts.
Adunyah
S E
SE
Department of Biochemistry, Meharry Medical College, Nashville, TN 37208.
D015153:Blotting, Western; D002478:Cells, Cultured; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D007938:Leukemia; D015473:Leukemia, Promyelocytic, Acute; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008970:Molecular Weight; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000378:metabolism; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism
D009363:Neoplasm Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D019000:Phosphotyrosine; D014443:Tyrosine; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor