Growth factor-induced signal transduction in adherent mammalian cells is sensitive to gravity

Epidermal growth factor (EGF) activates a well-characterized signal transduction cascade in a wide variety of cells. This activation leads to increased cell proliferation in most cell types. Among the early effects evoked by EGF are receptor clustering, cell rounding, and early gene expression. The influence of gravity on EGF-induced EGF receptor clustering and gene expression as well as on actin polymerization and cell rounding have been investigated in adherent A431 epithelial cells with the use of sounding rockets to create microgravity conditions. EGF-induced c-fos and c-jun expression decreased in microgravity. This was caused by alteration of the EGF receptor and protein kinase C-mediated signal transduction pathways. In contrast, neither the binding of EGF to the receptor nor the receptor clustering were changed under microgravity conditions, Because cell morphology was also modulated under microgravity conditions, and the growth factor-induced signal transduction cascades have been demonstrated to be linked to the actin microfilament system, it is tempting to suggest that the actin microfilament system constitutes the gravity-sensitive cell component.