Fibroblast growth factor 1 (FGF-1) is a potent angiogenic and neurotrophic factor whose structure lacks a classical signal sequence for secretion. Although the initiation of these biological activities involves the interaction between FGF-1 and cell surface receptors, the mechanism responsible for the regulation of FGF-1 secretion is unknown. We report that murine NIH 3T3 cells transfected with a synthetic gene encoding FGF-1 secrete FGF-1 into their conditioned medium in response to heat shock. The form of FGF-1 released by NIH 3T3 cells in response to increased temperature (42 degrees C, 2 hr) in vitro is not biologically active and does not associate with either heparin or the extracellular NIH 3T3 monolayer matrix. However, it was possible to derive biologically active FGF-1 from the conditioned medium of heat-shocked NIH 3T3 cell transfectants by ammonium sulfate fractionation. The form of FGF-1 exposed by ammonium sulfate fractionation is similar in size to cytosolic FGF-1 and can bind and be eluted from immobilized heparin similarly to the recombinant human FGF-1 polypeptide. Further, the release of FGF-1 by NIH 3T3 cell transfectants in response to heat shock is reduced significantly by both actinomycin D and cycloheximide. These data indicate that increased temperature may upregulate the expression of a factor responsible for the secretion of FGF-1 as a biologically inactive complex that requires an activation step to exhibit the biological activity of the extracellular polypeptide mitogen.
[1]
L V McIntire,et al.
Hydrodynamic shear stress and mass transport modulation of endothelial cell metabolism
,
1991,
Biotechnology and bioengineering.
[2]
H. Prats,et al.
Alternative initiation of translation determines cytoplasmic or nuclear localization of basic fibroblast growth factor
,
1991,
Molecular and cellular biology.
[3]
S. Lindquist,et al.
Reduced levels of hsp90 compromise steroid receptor action in vivo
,
1990,
Nature.
[4]
M. Barbacid,et al.
Molecular and biochemical characterization of the human trk proto-oncogene
,
1989,
Molecular and cellular biology.
[5]
Elizabeth A. Craig,et al.
A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides
,
1988,
Nature.
[6]
A. Levine,et al.
Immunological evidence for the association of p53 with a heat shock protein, hsc70, in p53-plus-ras-transformed cell lines
,
1987,
Molecular and cellular biology.