Lin Y Z, Yao S Y, Hawiger J
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2363, USA.
J Biol Chem. 1996 Mar 8;271(10):5305-8. doi: 10.1074/jbc.271.10.5305.
Fibroblast growth factor-1 (FGF-1) is a potent mitogen for mesoderm- and neuroectoderm-derived cell types in vitro. However, a mutant FGF-1 with deletion in its nuclear localization sequence (NLS, residues 21-27) is not mitogenic in vitro. We demonstrated that synthetic peptides containing this NLS were able to stimulate DNA synthesis in a FGF receptor-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 peptides during the entire G1 phase of the cell cycle. The mitogenic effect was specific for the NLS of FGF-1 because a peptide with double point mutations at lysine residues was inactive in stimulating DNA synthesis. Our results suggest that the NLS plays an important role in the mitogenic pathway initiated by exogenous FGF-1 by its direct involvement in the nuclear transport and signaling of internalized FGF-1.
成纤维细胞生长因子-1（FGF-1）在体外是中胚层和神经外胚层来源细胞类型的一种强效促有丝分裂原。然而，一种在其核定位序列（NLS，第21 - 27位氨基酸残基）缺失的突变型FGF-1在体外没有促有丝分裂作用。我们证明，含有该NLS的合成肽通过一种细胞可渗透肽导入技术导入活的NIH 3T3细胞后，能够以一种不依赖FGF受体的方式刺激DNA合成。这些肽对最大DNA合成的刺激在细胞周期的整个G1期都需要肽的存在。这种促有丝分裂作用对FGF-1的NLS具有特异性，因为在赖氨酸残基处有双点突变的一种肽在刺激DNA合成方面没有活性。我们的结果表明，NLS通过直接参与内化FGF-1的核转运和信号传导，在外源FGF-1启动的促有丝分裂途径中发挥重要作用。
