The precursor but not the mature form of IL1alpha blocks the release of FGF1 in response to heat shock.
Interleukin (IL)1alpha mediates proinflammatory events through its extracellular interaction with the IL1 type I receptor. However, IL1alpha does not contain a conventional signal peptide sequence that provides access to the endoplasmic reticulum-Golgi apparatus for secretion. Thus, we have studied the release of the precursor (p) and mature (m) forms of IL1alpha from NIH 3T3 cells. We have demonstrated that mIL1alpha but not pIL1alpha was released in response to heat shock with biochemical and pharmacological properties similar to those reported for the stress-mediated release pathway utilized by fibroblast growth factor (FGF)1. However, unlike the FGF1 release pathway, the IL1alpha release pathway appears to function independently of synaptotagmin (Syt)1 because the expression of a dominant-negative form of Syt1, which represses the release of FGF1, did not inhibit the release of mIL1alpha in response to temperature stress. Interestingly, whereas the expression of both mIL1alpha and FGF1 in NIH 3T3 cells did not impair the stress-induced release of either polypeptide, the expression of both pIL1alpha and FGF1 repressed the release of FGF1 in response to temperature stress. These data suggest that the release of mIL1alpha requires proteolytic processing of its precursor form and that mIL1alpha and FGF1 may utilize similar but distinct mechanisms for export.
Tarantini
F
F
Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074.
Micucci
I
I
Bellum
S
S
Landriscina
M
M
Garfinkel
S
S
Prudovsky
I
I
Maciag
T
T
D016475:3T3 Cells; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D002135:Calcium-Binding Proteins; D003847:Deoxyglucose / Q000494:pharmacology; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D018869:Heat-Shock Response; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D021381:Protein Transport; D017384:Sequence Deletion; D050863:Synaptotagmin I; D050857:Synaptotagmins; D014162:Transfection
D000631:Aminopyridines; D002135:Calcium-Binding Proteins; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D050863:Synaptotagmin I; C494311:Syt1 protein, mouse; C043830:interleukin 1 precursor; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D050857:Synaptotagmins; D020126:Brefeldin A; D003847:Deoxyglucose; C045742:amlexanox