The precursor of interleukin-1 alpha is phosphorylated at residue serine 90.

Mononuclear phagocytes release interleukin-1 (IL-1), a 17-kDa polypeptide with diverse biological activities. IL-1 is synthesized as a precursor (31 kDa) which lacks a signal sequence or hydrophobic domains that could facilitate transmembrane translocation. Possible postsynthetic modifications of IL-1 that might account for its cellular transport were examined. We found that lipopolysaccharide stimulated, but not unstimulated, murine macrophages incorporated 32PO4 into the IL-1 alpha precursor (31 kDa) predominantly at residue serine 90. Released IL-1 alpha (17 kDa) is not phosphorylated in agreement with peptide sequence data that the site of 32P incorporation is in the amino-terminal one-third of the precursor. Approximately 10% of the phosphorylated IL-1 alpha precursor is membrane bound and associated with a fraction enriched in lysosomal vesicles. Together these data suggest mechanisms by which the postsynthetic proteolysis of the IL-1 alpha precursor may be modified and cellular transport of IL-1 alpha is accomplished.