Nuclear activities of basic fibroblast growth factor: Potentiation of low-serum growth mediated by natural or chimeric nuclear localization signals

Marco Arese, Yan Chen, Robert Z. Florkiewicz, Anna Gualandris, Bin Shen, Daniel B. Rifkin

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Human basic fibroblast growth factor (FGF-2) occurs in four isoforms: a low molecular weight (LMW FGF-2, 18 kDa) and three high molecular weight (HMW FGF-2, 22, 22.5, and 24 kDa) forms, LMW FGF-2 is primarily cytoplasmic and functions in an autocrine manner, whereas HMW FGF-2s are nuclear and exert activities through an intracrine, perhaps nuclear, pathway. Selective overexpression of HMW FGF-2 forms in fibroblasts promotes growth in low serum, whereas overexpression of LMW FGF-2 does not. The HMW FGF-2 forms have two functional domains: an amino-terminal extension and a common 18-kDa amino acid sequence. To investigate the role of these regions in the intracrine signaling of HMW FGF-2, we produced stable transfectants of NIH 3T3 fibroblasts overexpressing either individual HMW FGF-2 forms or artificially nuclear-targeted LMW FGF-2. All of these forms of FGF-2 localize to the nucleus/nucleolus and induce growth in low serum. The nuclear forms of FGF-2 trigger a mitogenic stimulus under serum starvation conditions and do not specifically protect the cells from apoptosis. These data indicate the existence of a specific role for nuclear FGF-2 and suggest that LMW FGF-2 represents the biological messenger in both the autocrine/paracrine and intracrine FGF-2 pathways.

Original languageEnglish
Pages (from-to)1429-1444
Number of pages16
JournalMolecular Biology of the Cell
Volume10
Issue number5
Publication statusPublished - May 1999

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Nuclear Localization Signals
Fibroblast Growth Factor 2
Growth
Serum
Fibroblasts
Molecular Weight

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Nuclear activities of basic fibroblast growth factor : Potentiation of low-serum growth mediated by natural or chimeric nuclear localization signals. / Arese, Marco; Chen, Yan; Florkiewicz, Robert Z.; Gualandris, Anna; Shen, Bin; Rifkin, Daniel B.

In: Molecular Biology of the Cell, Vol. 10, No. 5, 05.1999, p. 1429-1444.

Research output: Contribution to journalArticle

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