ROLE OF THE NUCLEAR-LOCALIZATION SEQUENCE IN FIBROBLAST GROWTH FACTOR-1-STIMULATED MITOGENIC PATHWAYS

Citation
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
Citations number
24
Categorie Soggetti
Biology
ISSN journal
00219258
Volume
271
Issue
10
Year of publication
1996
Pages
5305 - 5308
Database
ISI
SICI code
0021-9258(1996)271:10<5305:ROTNSI>2.0.ZU;2-C
Abstract
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.