Nuclear Localization Of Fibroblast Growth Factor 13

Fibroblast growth factors (FGFs) make up a large family of polypeptide growth factorsthat are found in organisms ranging from nematodes to humans. In vertebrates, the 22members of the FGF family range in molecular mass from 17 to 34 kDa and share13-71% amino acid identity. FHFs bear strong sequence and structural similarity to FGFs.However, the biochemical and functional properties of FHFs are largely, if not totally,unrelated to those of FGFs. A homolog of FGF-13 (FHF2) has been molecularly clonedfrom cDNA library of rat dorsal root ganglion (DRG). The open reading frame of thisgene (2057 bp) encodes for a protein of 192 amino acids with amino acid identity greaterthan 99% to human FGF-13. In transiently transfected neurons and PC12 cells, ratFGF-13 accumulates in the nucleus. Then 8 truncated mutants of rat FGF-13 have beeninserted into plasmid pcDNA3.1/myc and transfected into PC12 cells. The results showedthat the five amino acids FLPKP close to the C-terminal was necessary for the nuclearaccumulation of FGF-13. We linked the nucleotide sequence encoded the five aminoacids (FLPKP) to the 3' end of SCLIP, and cloned into pEGFP-N2. TheSCLIP-FLPKP-EGFP protein entered into the nuclei of PC12 cells. Furthermore, our datashowed that the localization of FGF-13 in chick DRG neurons was a dynamic processthrough development. FGF-13 was mainly localized in cytoplasm at embryonic day 4 and5, but at later embryo day 7 and adult chick FGF-13 was found not only in cytoplasm butalso in nucleus. Our results indicate that the FLPKP sequence at c-terminal of FGF-13 isa non-classic nuclear localization signal, suggesting that FGF-13 may regulate thetranscription of other molecules through its nuclear localization.