Yz. Lin et al., ROLE OF THE NUCLEAR-LOCALIZATION SEQUENCE IN FIBROBLAST GROWTH FACTOR-1-STIMULATED MITOGENIC PATHWAYS, The Journal of biological chemistry, 271(10), 1996, pp. 5305-5308
Fibroblast growth factor-1 (FGF-1) is a potent mitogen for mesoderm- a
nd neuroectoderm-derived cell types in vitro. However, a mutant FGF-1
with deletion in its nuclear localization sequence (NLS, residues 21-2
7) is not mitogenic in vitro. We demonstrated that synthetic peptides
containing this NLS were able to stimulate DNA synthesis in a FGF rece
ptor-independent manner after they were delivered into living NIH 3T3
cells by a cell-permeable peptide import technique. The stimulation of
maximal DNA synthesis by these peptides required the presence of pept
ides during the entire G(1) phase of the cell cycle. The mitogenic eff
ect was specific for the NLS of FGF-1 because a peptide with double po
int mutations at lysine residues was inactive in stimulating DNA synth
esis. Our results suggest that the NLS plays an important role in the
mitogenic pathway initiated by exogenous FGF-1 by its direct involveme
nt in the nuclear transport and signaling of internalized FGF-1.