A carboxyl-terminal domain in fibroblast growth factor (FGF)-2 inhibits FGF-1 release in response to heat shock in vitro

J Biol Chem. 1997 Jan 10;272(2):1142-7. doi: 10.1074/jbc.272.2.1142.

Abstract

The fibroblast growth factor (FGF) prototypes, FGF-1 and FGF-2, lack a signal sequence, but both contain a nuclear localization sequence. We prepared a series of FGF-1 deletion mutants fused to the reporter gene, beta-galactosidase (beta-gal) and determined that a domain between residues 83 and 154 is responsible for FGF-1 cytosol retention in NIH 3T3 cells. Using a series of FGF-beta-gal chimeric proteins prepared by the shuffling of cassette-formatted synthetic FGF prototype genes, we were able to demonstrate that the nuclear localization sequence from the 5'-CUG region of FGF-2 is not able to direct the nuclear association of FGF-1 due to its inability to repress the function of the FGF-1 cytosol retention domain. We also observed that while the FGF-1:beta-gal chimera was released in response to heat shock, the FGF-2:beta-gal protein was not. Further, replacement of the FGF-1 cytosol retention domain with the corresponding domain from FGF-2 repressed the release of the chimeric protein. These data suggest that the specificity of the stress-induced secretion pathway for FGF-1 involves a carboxyl-terminal domain that is absent in FGF-2 and that the FGF-1 secretion pathway does not restrict the release of high molecular weight forms of FGF-1.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Fibroblast Growth Factor 1 / chemistry
  • Fibroblast Growth Factor 1 / genetics
  • Fibroblast Growth Factor 1 / metabolism*
  • Fibroblast Growth Factor 2 / chemistry*
  • Fibroblast Growth Factor 2 / metabolism
  • Hot Temperature
  • Mice
  • Molecular Weight
  • Mutagenesis, Site-Directed
  • Open Reading Frames
  • Plasmids / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Sequence Deletion
  • Structure-Activity Relationship

Substances

  • Recombinant Fusion Proteins
  • Fibroblast Growth Factor 2
  • Fibroblast Growth Factor 1