Translokin is an intracellular mediator of FGF-2 trafficking

• Published in: Nature cell biology Vol. 5; no. 5; pp. 433 - 439
• Main Authors: Prats, Hervé, Bossard, Carine, Laurell, Henrik, Van den Berghe, Loïc, Meunier, Sylvain, Zanibellato, Catherine
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.05.2003
• Subjects: 3T3 Cells; Active Transport, Cell Nucleus - genetics; Amino Acid Sequence - genetics; Animals; Antibodies; Base Sequence - genetics; Carrier Proteins; Cell Nucleus - genetics; Cellular signal transduction; COS Cells; Cytoplasm - genetics; Cytoplasm - metabolism; Eukaryotic Cells - cytology; Eukaryotic Cells - metabolism; Fibroblast Growth Factor 1 - genetics; Fibroblast Growth Factor 1 - metabolism; Fibroblast Growth Factor 2 - genetics; Fibroblast Growth Factor 2 - metabolism; Fibroblast growth factors; Fluorescent Antibody Technique; Genetic aspects; Intermediate filament proteins; Kinases; Localization; Mice; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - isolation & purification; Microtubule-Associated Proteins - metabolism; Microtubules - genetics; Microtubules - metabolism; Mitosis - genetics; Molecular Sequence Data; Mutation - genetics; Nuclear Proteins; Physiological aspects; Protein Transport - genetics; Proteins; Prototypes; Recombinant Fusion Proteins - genetics; RNA Interference - physiology; Translocation; France
• ISSN: 1465-7392; 1476-4679; 1476-4679
• DOI: 10.1038/ncb979

Basic fibroblast growth factor (bFGF or FGF-2) exerts its pleiotropic activities both as an exogenous and an intracellular factor. FGF-1 and FGF-2 are prototypes for this dual signalling, but the mechanisms of their intracellular actions remain unknown. Here we show that Translokin, a cytoplasmic protein of relative molecular mass 55,000 (Mr 55K), interacts specifically with the 18K form of FGF-2. Translokin is ubiquitously expressed and colocalizes with the microtubular network. As Translokin does not interact with FGF-1, we used a strategy based on FGF-1-FGF-2 chimaeras to map the interacting regions in FGF-2 and to generate Nb1a2, a non-interacting variant of FGF-2. Although most of the FGF-2 properties are preserved in Nb1a2, this variant is defective in intracellular translocation and in stimulating proliferation. The fusion of a nuclear localization signal to Nb1a2 restores its mitogenic activity and its nuclear association. Inhibiting Translokin expression by RNA interference reduces the translocation of FGF-2 without affecting the intracellular trafficking of FGF-1. Our data show that the nuclear association of internalized FGF-2 is essential for its mitogenic activity and that Translokin is important in this translocation pathway.