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Translokin is an intracellular mediator of FGF-2 trafficking

Nature Cell Biology volume 5, pages 433–439 (2003)Cite this article

Abstract

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.

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Figure 1: Characterization of Translokin, an FGF-2-interacting protein.
Figure 2: Specific and direct interaction between Translokin and FGF-2.
Figure 3: Characterization of FGF-2–FGF-1 chimaeras.
Figure 4: FGF-2 intracellular localization.
Figure 5: Recovery of Nb1a2 mitogenic activity and inhibition of FGF-2.

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Acknowledgements

We thank G. Bouche for HA–FGF-2 plasmid; D. Bresson and B. Knibiehler for technical advice; and B. Bugler, C. Touriol, A. C. Prats and F. Bayard for discussions and critically reading the manuscript. C.B. was supported by the Association pour la Recherche contre le Cancer; H.L. was supported by an INSERM fellowship. This work was supported by the Association pour la Recherche contre le Cancer and the Ligue Nationale contre le Cancer.

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  1. INSERM U589, IFR 31, Institut Louis Bugnard, CHU Rangueil, Bat L3, Toulouse, 31403 Cedex 04, France

    Carine Bossard, Henrik Laurell, Loïc Van den Berghe, Sylvain Meunier, Catherine Zanibellato & Hervé Prats

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Correspondence to Hervé Prats.

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Figure S1. Translokin expression is ubiquitous (PDF 833 kb)

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Bossard, C., Laurell, H., Van den Berghe, L. et al. Translokin is an intracellular mediator of FGF-2 trafficking. Nat Cell Biol 5, 433–439 (2003). https://doi.org/10.1038/ncb979

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