Structure and function of membrane IL-1.
Both interleukin-1 alpha (IL-1 alpha) and IL-1 beta are initially translated as approximately Mr 30,000 polypeptides, lacking hydrophobic or signal sequence that could facilitate transmembrane translocation and release of mature IL-1 (Mr 17,500). The current study utilizes an antiserum specific for murine IL-1 alpha in order to investigate membrane associated IL-1 alpha polypeptides and possible postsynthetic modifications of the IL-1 alpha precursor, that might account for its intracellular transport. Cell surface iodination of endotoxin stimulated murine macrophages allowed the detection of IL-1 molecules in size similar to the IL-1 alpha precursor (Mr 33,000). Membrane bound IL-1 alpha was sensitive to degradation by serine esterase activity to yield IL-1 peptides of Mr 16,000 to 18,000. Endotoxin stimulated macrophages, but not unstimulated cells, incorporated 32PO4 into the IL-1 alpha precursor. The phosphate label of the IL-1 alpha precursor is resistant to hydroxylamine and alkaline phosphatase treatment. Released IL-1 is not phosphorylated. Approximately 10% of the phosphorylated IL-1 alpha precursor is membrane bound and associated with fractions enriched in lysosomal vesicles. These data are consistent with a model for mIL-1 expression, in which pro IL-1 alpha is post-synthetically modified to achieve intracellular transport and further suggest that mIL-1 may be a prerequisite for the release of IL-1.
Beuscher
H U
HU
Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, Children's Hospital, St. Louis, Missouri.
Colten
H R
HR
D000818:Animals; D002462:Cell Membrane / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D004731:Endotoxins / Q000494:pharmacology; D007375:Interleukin-1 / Q000032:analysis* / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008970:Molecular Weight; D010766:Phosphorylation; D013347:Subcellular Fractions / Q000276:immunology
D004731:Endotoxins; D007375:Interleukin-1