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. These different species of molecular masses of 18, 21.5, 22, and 24 kDa are all translated via the use of alternate initiation codons. The three forms of HMW FGF-2 initiate at CUGs codons, whereas the 18 kDa form initiates at an AUG codon. The entire 18 kDa sequence is contained within 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 cytosol, a significant fraction of the HMW FGF-2 has a nuclear location. The nuclear localization of HMW FGF-2 is determined by amino acid residues in the amino-terminal extended sequence. The residues required for nuclear localization appear to be RG repeats that are found at multiple sites within the amino-terminal extension of HMW FGF-2. The nuclear localization of HMW FGF-2 suggested that these species may have unique properties. By selecting permanent transfectants of 3T3 cells expressing HMW, 18 kDa FGF-2, or all forms of FGF-2, we have found that HMW 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Rifkin
D B
DB
Department of Cell Biology, New York University Medical Center, New York 10016.
Moscatelli
D
D
Roghani
M
M
Nagano
Y
Y
Quarto
N
N
Klein
S
S
Bikfalvi
A
A
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003062:Codon; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000502:physiology*; D006493:Heparin / Q000494:pharmacology*; D051379:Mice; D008970:Molecular Weight; D016297:Mutagenesis, Site-Directed; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D003062:Codon; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D006493:Heparin