Zinc has a strong influence on the function of the immune system and is a driving factor for immune cell development. In this regard, studies revealed cell type specific effects of zinc. During zinc deficiency for example, development and activity of myeloid cells seems to be prioritized at the cost of cells from the lymphoid lineage. In T-cells, the altered proliferation was found to be due to zinc's effect on IL-2-induced signaling processes, but in contrast to lymphoid cells, effects of zinc homeostasis on growth-factor-induced signaling in myeloid cells have not been investigated yet. The granulocyte-macrophage colony-stimulating factor (GM-CSF) is one of the major factors inducing monopoiesis. Considering the structural similarities between the GM-CSF receptor and those of the IL-receptor family as well as a similar set of signaling molecules involved, an impact of zinc on the GM-CSF signaling seems to be likely. Therefore, the effect of zinc on GM-CSF-induced signaling molecules was investigated here, using U937 cells as a model myeloid cell line. GM-CSF stimulation significantly increased STAT5 phosphorylation which was prevented completely by pre-incubation with zinc and pyrithione. U937 cells showed a strong pre-activation regarding c-Raf, which was significantly decreased by zinc and pyrithione incubation, independently from GM-CSF stimulation. As current literature was not sufficient to explain the observed effects, we hypothesized an altered receptor-complex assembly. As membrane composition and plasticity, subsumed under the term of membrane fluidity, was found to affect receptor multimerization, the impact of zinc on membrane fluidity was considered as a completely novel approach. Indeed, addition of zinc also decreased GM-CSFR expression on the cell surface and most interestingly altered membrane fluidity. In conclusion, we hypothesize that the incubation with zinc causes an alteration of membrane fluidity that hinders efficient receptor assembly as well as phosphorylation of signal molecules and therefore signal transduction.