[Activation of the cell proliferation program by acidic fibroblast growth factor (aFGF)]

Abstract

Acidic fibroblast growth factor belongs to the fibroblast growth factor family. It is a potent mitogenic agent. The growth factor acts through activation of specific cell-surface receptors leading to intracellular tyrosine phosphorylation cascade. In addition to its extracellular action, however, there are reports indicating that aFGF enters cells and that it has an intracellular function as well. Using different experimental approaches it was found that: 1) aFGF can stimulate DNA synthesis in cells without specific receptors when is translocated into cells as a fusion protein with diphtheria toxin, 2) the growth factor as such is able to enter cells expressing FGF receptors and localize in nuclei, and 3) an intracellular protein, which specifically binds only to mitogenic aFGF was found as well. Therefore it might be concluded, that transport of the growth factor from the cell-surface into the nucleus is an important event in the mechanism of stimulation of DNA synthesis and activation the proliferation program during aFGF treatment.