Serum alleviates the requirement of the granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced Ras activation for proliferation of BaF3 cells

Publisher Website
Google Scholar
Abstract
Deletion analysis of the β subunit of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor previously defined two cytoplasmic regions required for distinct signaling. The membrane-proximal region is responsible for induction of c-myc and pim-1, and is indispensable for GM-CSF-dependent proliferation of mouse BaF3 transfectants. The distal region is required for activation of Ras, Raf-1, MAP kinase and p70 S6 kinase as well as induction of c-fos and c-jun, but is dispensable for GM-CSF-dependent proliferation of transfectants under normal culture conditions containing serum. Here we show that signals induced by the distal region of the β subunit are also required for proliferation. GM-CSF supported proliferation of BaF3 transfectants expressing the normal β subunit, even in serum-free medium. However, in the absence of serum, GM-CSF did not support proliferation of BaF3 transfectants that have the β deletion mutants lacking the distal region. Serum-induced activation of Ras, phosphorylation of MAP kinase and expression of c-fos in parental BaF3 cells and antisense oligonucleotide against c-raf blocked DNA synthesis of BaF3 cells. These results indicate that proliferation of BaF3 cells requires signals induced by the proximal as well as the distal region of the β subunit of the GM-CSF receptor, and that serum alleviates the requirement of signals induced by the distal region.