Further aspects of IL-1 beta secretion revealed by transfected monkey kidney cells.
Because the cytokine interleukin-1 beta (IL-1 beta) lacks a classical hydrophobic signal sequence, it has been unclear how it is released from cells, and whether release proceeds via a novel mechanism or through non-specific leakage. To address this issue, we have examined the secretion of the recombinant forms of human IL-1 beta from COS monkey kidney cells, which express low levels of endogenous IL-1 beta. Four proteins were expressed: precursor and mature IL-1 beta and precursor and mature IL-1 beta fused to an amino terminal hydrophobic signal sequence from human tissue plasminogen activator. By monitoring the appearance of a known cytosolic protein (ATP citrate lyase) in the medium, we find that the unmodified IL-1 beta s are non-specifically released in very small quantities from the cytosol. On the other hand, the signal sequence-modified IL-1 beta s are glycosylated and efficiently secreted by the ER/Golgi pathway. The secreted, modified-mature protein is also biologically active, suggesting that this pathway has been bypassed for reasons other than maintaining the structural integrity of IL-1 beta. More likely the alternative pathway is a critical aspect of IL-1 biology. The differences in kinetics and quantity of IL-1 beta release from monocytic and COS cells suggest that COS cells lack critical components for the rapid release seen in monocytes.
Krasney
P A
PA
Department of Molecular Genetics, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406.
Young
P R
PR
D000818:Animals; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D000882:Haplorhini / Q000235:genetics; D007375:Interleukin-1 / Q000737:chemistry / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000737:chemistry; D014162:Transfection / Q000235:genetics*
D007375:Interleukin-1; D021382:Protein Sorting Signals