Influence of compounds affecting synthesis, modification and transport of proteins on the expression and release of interleukin-2 receptor.
One of the most central events during lymphocyte activation is the synthesis and release of IL-2. IL-2 induces the synthesis and expression of the IL-2 receptor alpha-chain (IL-2R) on the lymphocyte as well as the release of a truncated form of IL-2R (sIL-2R). The two proteins are identical except for the absence of the transmembrane and intracellular part on sIL-2R. We have in an in vitro model investigated the influence of certain compounds, affecting different parts of the proliferative response, on the release and expression of IL-2R. We found the generation of the two molecules to have different sensitivity to blocking of protein synthesis, glycosylation, microtubular assembly and proteolytic activity. However, blocking of intracellular transport from Golgi to the endoplasmic reticulum, disassembly of actin filaments and disturbances in the intracellular sodium/calcium balance had identical effects on expression and release of the respective IL-2R. These findings indicate a more complex and specific mechanism behind the generation of sIL-2R than simply by shedding through the action of proteases on the membrane-bound IL-2R.
Karlsson
H
H
University of Lund, Department of Medical Microbiology, Sweden.
Nässberger
L
L
D007611:Aprotinin / Q000494:pharmacology; D020126:Brefeldin A; D002478:Cells, Cultured; D003517:Cyclopentanes / Q000494:pharmacology; D003572:Cytochalasins / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008985:Monensin / Q000494:pharmacology; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000187:drug effects* / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000187:drug effects*; D014748:Vinca Alkaloids / Q000494:pharmacology
D003517:Cyclopentanes; D003572:Cytochalasins; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D015375:Receptors, Interleukin-2; D014748:Vinca Alkaloids; D020126:Brefeldin A; D008985:Monensin; D007611:Aprotinin