S100A13 participates in the release of fibroblast growth factor 1 in response to heat shock in vitro.
S100A13, a member of the S100 gene family of Ca(2+)-binding proteins has been previously characterized as a component of a brain-derived heparin-binding multiprotein aggregate/complex containing fibroblast growth factor 1 (FGF1). We report that while expression of S100A13 in NIH 3T3 cells results in the constitutive release of S100A13 into the extracellular compartment at 37 degrees C, co-expression of S100A13 with FGF1 represses the constitutive release of S100A13 and enables NIH 3T3 cells to release S100A13 in response to temperature stress. S100A13 release in response to stress occurs with kinetics similar to that observed for the stress-induced release of FGF1, but S100A13 expression is able to reverse the sensitivity of FGF1 release to inhibitors of transcription and translation. The release of FGF1 and S100A13 in response to heat shock results in the solubility of FGF1 at 100% (w/v) ammonium sulfate saturation, and the expression of a S100A13 deletion mutant lacking its novel basic residue-rich domain acts as a dominant negative effector of FGF1 release in vitro. Surprisingly, the expression of S100A13 also results in the stress-induced release of a Cys-free FGF1 mutant, which is normally not released from NIH 3T3 cells in response to heat shock. These data suggest that S100A13 may be a component of the pathway for the release of the signal peptide-less polypeptide, FGF1, and may involve a role for S100A13 in the formation of a noncovalent FGF1 homodimer.
Landriscina
M
M
Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine 04074, USA.
Soldi
R
R
Bagalá
C
C
Micucci
I
I
Bellum
S
S
Tarantini
F
F
Prudovsky
I
I
Maciag
T
T
D016475:3T3 Cells; D000818:Animals; D002135:Calcium-Binding Proteins / Q000502:physiology*; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D018869:Heat-Shock Response; D006493:Heparin / Q000378:metabolism; D051379:Mice; D014176:Protein Biosynthesis; D009418:S100 Proteins; D012756:Sheep; D014158:Transcription, Genetic
D002135:Calcium-Binding Proteins; D009418:S100 Proteins; C489950:S100a3 protein, mouse; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D006493:Heparin