Effect of granulocyte-macrophage colony-stimulating factor and interleukin 3 on the v-src oncogene. Inhibition of tyrosine kinase activity in the absence of changes in gene expression.
Three cloned murine interleukin 3 (IL-3)-dependent cell lines have been converted to interleukin 2 (IL-2) or granulocyte-macrophage colony-stimulating factor (GM-CSF) growth-dependent states. FD.C/1 32Dcl-23 and GM cells grown and maintained as IL-3-dependent cell lines, and cells grown with GM-CSF have been infected with a murine recombinant retrovirus containing the v-src oncogene, and grown as lymphokine-independent cell lines. There is a significant increase in tyrosine kinase activity in cells which become lymphokine-independent. FD.C/1 and 32Dcl-23 cells maintained as IL-2-dependent cells lines and infected with the same virus did not grow as IL-2-independent cells. The lymphokine-independent cells FD.C/1src, 32Dsrc, and GMsrc all expressed high levels of tyrosine kinase activity, ranging from 5- to 20-fold more than levels measured in virus-infected cell lines maintained as IL-2-dependent cells. The exposure of FD.C/1src and 32Dsrc cells to IL-3, and GMsrc cells to IL-3 or GM-CSF, resulted in significant decreases in tyrosine kinase activity. These changes were rapidly reversed by removal of IL-3 or GM-CSF from these cells. However, the synthesis of v-src-specific RNA was not affected by the presence of IL-3 or GM-CSF in these cell lines. The biochemical pathways activated by IL-3 or GM-CSF inhibit the activity of the tyrosine kinase encoded by the v-src oncogene without altering gene transcription.
Watson
J D
JD
Department of Immunobiology, School of Medicine, University of Auckland, New Zealand.
Jenkins
D R
DR
Eszes
M
M
Leung
E
E
D000818:Animals; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006098:Granulocytes / Q000032:analysis / Q000201:enzymology*; D007377:Interleukin-3 / Q000494:pharmacology*; D008222:Lymphokines / Q000494:pharmacology; D008264:Macrophages / Q000032:analysis / Q000201:enzymology*; D051379:Mice; D009857:Oncogenes / Q000187:drug effects*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012367:RNA, Viral / Q000032:analysis
D003115:Colony-Stimulating Factors; D007377:Interleukin-3; D008222:Lymphokines; D012367:RNA, Viral; D011505:Protein-Tyrosine Kinases