Structural Characterization and Biological Functions of Fibroblast Growth Factor

Abstract

BASIC AND acidic fibroblast growth factors (FGFs) are closely related molecules that show a similar range of biological activities. They differ, however, in some of their physical and chemical properties and in their tissue distribution (1). Basic FGF [bFGF isoelectric point (pi) 9.6] was first identified by its ability to cause the proliferation and phenotypic transformation of BALB/c 3T3 fibroblasts (2, 3). Acidic FGF (aFGF, pi 5.6) was first identified by its ability to cause proliferation and delayed differentiation of myoblasts (4); it was later rediscovered on the basis of its ability to stimulate endothelial cell proliferation (5, 6). As expected from their structural relationship, both FGF and aFGF interact with the same receptor (7), thereby having similar, if not identical, properties. In contrast to aFGF, which has a cellular distribution more restricted than bFGF, many different cells synthesize bFGF, and essentially all have a specific high affinity receptor for this peptide. bFGF is thus a fundamental regulatory molecule, acting by both autocrine and paracrine mechanisms. Recent studies indicate an important role for both bFGF and aFGF in cells of vascular, nervous, and connective tissue. bFGF and aFGF are multifunctional, since they can either stimulate proliferation and induce or delay differentiation (8). They stimulate other critical processes in cell function as well. As is true for most peptide growth factors, the basic molecular mechanism of action of FGFs is at present unknown. Nevertheless, so many new and varied functions have now been described for bFGF and could be extrapolated to aFGF that, at present, one must consider these two closely related peptides to be general mediators of regulation in the cell, and one of special importance for positive control of cell growth and differentiation.