Interferon-gamma and tumor necrosis factor-alpha enhance p60src expression in human macrophages and myelomonocytic cell lines.
We investigated modulation of p60src expression in human mononuclear phagocytes. By analysis of [35S]methionine-labelled cells we found that synthesis of p60src is higher in human monocytes compared to macrophages derived from in vitro cultivation of monocytes. Western blot analysis showed that expression of p60src in monocyte-derived macrophages can be enhanced if monocytes are differentiated into macrophages in the presence of interferon-gamma (IFN-gamma), or tumor necrosis factor-alpha (TNF-alpha). Enhanced p60src expression caused by IFN-gamma or TNF-alpha correlated with an enhanced autophosphorylating kinase activity assayed in anti-p60src immune precipitates. In vivo phosphorylation of p60src and analysis of phosphopeptides by tryptic digestion showed that treatment with cytokines did not affect the pattern of phosphorylation of distinct phosphopeptides. The human monocytic cell lines, U937 and HL-60, induced to differentiate along the monocytic pathway by IFN-gamma, or a combination of IFN-gamma and TNF-alpha, expressed higher amounts of the p60src, but not of the p59fyn or p62yes, kinase activity. These findings show that p60src is modulated in the course of differentiation of human monocytes to macrophages, and that macrophage-activating cytokines increase p60src expression in human monocyte-derived macrophages.
Sorio
C
C
Institute of General Pathology, University of Verona, Italy.
Melotti
P
P
Dusi
S
S
Berton
G
G
D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015479:Leukemia, Myelomonocytic, Acute / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016392:Proto-Oncogene Proteins pp60(c-src)