Summary

The seminal work that began in the 1970s (Armelin, 1973), (Gospodarowicz, 1974) and (Gospodarowicz, 1975) and early 1980s (Bohlen et al., 1984) with the purification of a single polypeptide posessing a novel bioactivity has evolved dramatically with the discovery of 23 genes encoding a family of structurally (as well as functionally) related polypeptides, the fibroblast growth factors (FGFs). As a family, FGFs act in a paracrine or autocrine manner and display a characteristic affinity for heparin (Gospodarowicz, et al, 1984) and (Shing, et al, 1984) which is critical for interactions with signal-transducing receptors (Ornitz, 2000a) and (Wiesmann and de Vos, 1999). In addition to their property of promoting cell growth and their ability to induce a mitogenic response (Burgess and Maciag, 1989), FGFs also stimulate cell migration (Presta et al., 1986), angiogenesis (Gospodarowicz, et al, 1979), (Folkman and Klagsbrun, 1987), (Klagsbrun and D'Amore, 1991) and (Montesano, et al, 1986), vasculogenesis (Krah et al., 1994), hematopoietic development (Faloon et al., 2000), wound healing and tissue repair (Davidson et al., 1985), differentiation (Kimelman and Kirschner, 1987), (Kimelman and Maas, 1992) and (Olwin, et al, 1994), transformation (Sasada et al., 1988), and morphogenesis (Dono and Zeller, 1994), (Niswander, et al, 1994) and (Olwin, et al, 1994). To mediate such multifarious activities, FGFs function in concert with a similarly complex family of cognate signal-transducing receptors (FGFRs) and nontransducing heparan sulface-containing proteoglycans (HSPGs), the cysteine-rich receptor (CFR), and binding proteins (BPs). Furthermore, FGFs and their receptors exhibit remarkably varied mechanisms regulating their expression and/or bioavailability. These mechanisms occur at multiple levels of gene expression, including transcription, translation, intracellular protein trafficking, extracellular matrix localization, and release. For additional perspectives into the FGF family, a series of reviews can be referred to for information not provided herein (Basilico and Moscatelli, 1992), (Delrieu, 2000), (Martin, 1998), (McKeehan, et al, 1998), (Nugent and Izzo, 2000), (Okada-Ban, et al, 2000) and (Szebenyi and Fallon, 1999).