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Thrombin cleaves the high molecular weight forms of basic fibroblast growth factor (FGF-2): a novel mechanism for the control of FGF-2 and thrombin activity

Oncogene volume 27, pages 2594–2601 (2008)Cite this article

Abstract

The fgf-2 gene encodes low molecular weight (LMW, 18 kDa) and high molecular weight (HMW, 22–24 kDa) forms that originate from alternative translation of a single mRNA and exhibit diverse biological functions. HMW fibroblast growth factor-2 (FGF-2) inhibits cell migration and induces cell transformation or growth arrest in a cell type- and dose-dependent fashion. Conversely, LMW FGF-2 upregulates both cell proliferation and migration in most cell types. Although transcriptional and translational regulation of HMW and LMW FGF-2 has been extensively investigated, little is known about post-translational control of their relative expression. Here we report that thrombin, a key coagulation factor and inflammatory mediator, cleaves HMW FGF-2 into an LMW FGF-2-like form that stimulates endothelial cell migration and proliferation. The effect of thrombin on these cell functions requires HMW FGF-2 cleavage. This post-translational control mechanism adds a novel level of complexity to the regulation of FGF-2, and links the activities of thrombin and FGF-2 in patho-physiological processes in which both molecules are expressed.

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Acknowledgements

This work was supported by funds from the Department of Cardiothoracic Surgery of NYU School of Medicine and in part by the NIH grant 5 R01 HL70203-01 (PM).

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Authors and Affiliations

  1. Department of Cardiothoracic Surgery, The Seymour Cohn Cardiovascular Research Laboratory, New York University School of Medicine, New York, NY, USA

    P-J Yu, G Ferrari, L Pirelli, A C Galloway, P Mignatti & G Pintucci

  2. Department of Cell Biology, New York University School of Medicine, New York, NY, USA

    P Mignatti

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  1. P-J Yu
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  2. G Ferrari
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  3. L Pirelli
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  4. A C Galloway
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  5. P Mignatti
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  6. G Pintucci
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Correspondence to G Pintucci.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Yu, PJ., Ferrari, G., Pirelli, L. et al. Thrombin cleaves the high molecular weight forms of basic fibroblast growth factor (FGF-2): a novel mechanism for the control of FGF-2 and thrombin activity. Oncogene 27, 2594–2601 (2008). https://doi.org/10.1038/sj.onc.1210899

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