Dissection of the Role of the Different bFGF Isoforms

Several forms of bFGF have been described in most bFGF producing cell types (75). They result from an alternative initiation of translation of one single mRNA: at an AUG codon (18-kDa form) or at three different upstream CUG (24-, 21.5- and 21-kDa forms) (76). In vitro, the relative amount ofthe four bFGF forms varies according to the cell type: the higher molecular weight CUG-initiated forms are mainly detected in transformed cell lines, whereas normal cell types mostly overproduce the 18-kDa form (77). Different roles have been described for the low and high molecular weight forms. Although constitutive expression of the 18-kDa form leads to an in vitro transformed phenotype, constitutive expression of 21-, 21.5-, and 24-kDa forms is immortalizing (78) after transfection with the respective cDNA. CUG initiated forms contain an amino-terminal sequence responsible for nuclear localization of these proteins (79), whereas the 18-kDa form is mainlycytoplasmic (75,79). Recentresultshave demonstratedthatthe 18-kDaformmay be externalized and acts via specific cell surface receptors, the higher molecular weight CUG initiated forms on the other hand modulate cell proliferation by an intracellular mechanism independent of membrane receptors (80).

Was this article helpful?

0 0

Post a comment