STUDIES ON FGF-2 - NUCLEAR-LOCALIZATION AND FUNCTION OF HIGH-MOLECULAR-WEIGHT FORMS AND RECEPTOR-BINDING IN THE ABSENCE OF HEPARIN

Multiple forms of FGF-2 have been shown to exist in many cell types. T hese different species of molecular masses of 18, 21.5, 22, and 24 kDa are all translated via the use of alternate initiation codons. The th ree forms of HMW FGF-2 initiate at CUGs codons, whereas the 18 kDa for m initiates at an AUG codon. The entire 18 kDa sequence is contained w ithin the larger forms of HMW FGF-2 as the AUG codon is 3' to the CUG codons. Although the 18 kDa form FGF-2 is localized primarily in the c ytosol, a significant fraction of the HMW FGF-2 has a nuclear location . The nuclear localization of HMW FGF-2 is determined by amino acid re sidues in the amino-terminal extended sequence. The residues required for nuclear localization appear to be RG repeats that are found at mul tiple sites within the amino-terminal extension of HMW FGF-2. The nucl ear localization of HMW FGF-2 suggested that these species may have un ique properties. By selecting permanent transfectants of 3T3 cells exp ressing HMW, 18 kDa FGF-2, or all forms of FGF-2, we have found that H MW FGF-2 can endow cells with a phenotype different from that of cells expressing 18 kDa FGF-2. These cells are transformed by what appears to be the intracellular action of HMW FGF-2. The interaction of FGF-2 with heparin has also been examined. Contrary to other reports claimin g that FGF-2 required heparin or heparan-sulfate for interaction with its high-affinity receptor, we have found that FGF-2 binds to its rece ptor in the absence of glycosaminoglycans, and that this binding activ ates the receptor. (C) 1994 Wiley-Liss, Inc.