Recent developments in the cell biology of basic fibroblast growth factor

I N the past four years there has been an enormous increase in research involving basic fibroblast growth factor (FGF) t as a result of the development of effective methods for the isolation of the protein and the availability of characterized nucleic acid probes, specific antibodies, and recombinant growth factor. Several reviews have been published describing much of the basic biology of acidic FGF (aFGF) and basic FGF (bFGF) (5, 25, 33). Therefore, in this mini-review we have fo-cused on specific areas in bFGF biology in which uncertainties exist. For simplicity, we have confined this review to bFGF. However, some of the questions concerning bFGF also apply to aFGF and are discussed. History FGF was originally identified as an activity in extracts of pituitary and brain that stimulated the growth of 3T3 cells (3, 23). The activity was shown to be due to two proteins. One of them, aFGF, had an acidic pI (5.6) and eluted from hep-arin-Sepharose with I M NaC1 (34, 65). The second, bFGF, had a basic pI (>9.0), eluted from heparin-Sepharose at 1.5 M NaCI, and had 55 % sequence homology to aFGF (14). The introduction of heparin-affinity chromatography facilitated the isolation of sufficient quantities of bFGF for structural studies. Bovine pituitary bFGF was found to be a 146-amino acid protein with a molecular weight of 16,400 (14), while human placental bFGF had 157 amino acids with a molecular weight of 17,500 (63). However, smaller forms of both bovine and human bFGF have been identified which apparently arise by truncation at the amino terminus (43). The shortest molecule that retained biological activity lacked the first 15 amino acids present in bovine pituitary bFGF (14). In some instances these truncated forms of bFGF seem to be generated by proteases released during the isolation procedure (31). The 146-amino acid bovine bFGF may, itself, derive from a larger molecule since extraction of pituitaries in the presence of protease inhibitors yielded a larger form (66). This idea is supported by data on the potential transla-1. Abbreviations used in this paper: aFGE acidic fibroblast growth factor; bFGE basic fibroblast growth factor; ECM, extracellular matrix; FGE fibro-blast growth factor; GAG, glyeosaminoglyeans; HSPG, heparan sulfate pro-teoglyeans. tion initiation sites identified from the eDNA for bFGF (see below). The amino acid sequence of bFGF has some unusual attributes , bFGF contains four cysteines. Two are conserved among all members of the FGF family (71) …