Involvement of basic fibroblast growth factor NH2 terminus in nuclear accumulation. 1994

V Patry, and E Arnaud, and F Amalric, and H Prats
Institut Louis Bugnard, Institut National de la Santé et la Recherche Médicale Unité 397, CHU Rangueil, Toulouse, France.

The human basic Fibroblast Growth Factor (bFGF) gene was shown to encode four polypeptides by an alternative use of initiation codons (three CUG and one AUG). In this report, we present a comparative study of the fate and intracellular localization of individual bFGF isoforms. For this purpose, we have produced the various bFGF isoforms in E. coli and purified them to homogeneity: the 210 amino acid form initiated at CUG1 that contains a nuclear localization sequence (NLS), the 155 amino acid form (AUG-mediated initiation) and the 146 amino acid form (processed form extracted from tissues). While the different bFGFs were taken up by the cell with equal efficiency, more of the 210 amino acid form accumulated in the nucleus and represented 36% of the internalized bFGF compared with 15% in the others. A chimeric protein containing the minimal SV40 Large T NLS (SV40NLS) fused to the 155 amino acid bFGF form (SVbFGF) behaves like the native 155 amino acid form, indicating that nuclear accumulation of exogenous bFGF is not mediated by the NLS-associated function. These results suggest that the amino-terminal part of the 210 amino acid bFGF contains a sequence responsible for its nuclear retention. Bioactivities of the different forms were tested on adult bovine aortic endothelial (ABAE) cells. The bFGF degradation pathways, mitogenic activity and stimulation of rRNA synthesis appeared to be the same for all bFGFs but the stimulation of plasminogen activator was enhanced by the 210 amino acid form and correlated with nuclear accumulation.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D008970 Molecular Weight The sum of the weight of all the atoms in a molecule. Molecular Weights,Weight, Molecular,Weights, Molecular
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D010960 Plasminogen Activators A heterogeneous group of proteolytic enzymes that convert PLASMINOGEN to FIBRINOLYSIN. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. Extrinsic Plasminogen Activators,Plasminogen Activator,Uterine-Tissue Plasminogen Activator,Uterine Tissue Plasminogen Activator
D002417 Cattle Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor. Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D002467 Cell Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed) Cell Nuclei,Nuclei, Cell,Nucleus, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003001 Cloning, Molecular The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells. Molecular Cloning
D004591 Electrophoresis, Polyacrylamide Gel Electrophoresis in which a polyacrylamide gel is used as the diffusion medium. Polyacrylamide Gel Electrophoresis,SDS-PAGE,Sodium Dodecyl Sulfate-PAGE,Gel Electrophoresis, Polyacrylamide,SDS PAGE,Sodium Dodecyl Sulfate PAGE,Sodium Dodecyl Sulfate-PAGEs
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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