Receptor mediated endocytosis and intracellular fate of interleukin 1.
We have studied the receptor mediated endocytosis of interleukin 1 (IL1) by the murine thymoma cell line EL4. These cells express the Type I IL1 receptor which binds its ligand with both high (Kd = 65 pM) and low affinity (Kd = 14.5 nM). We have shown that the two affinity states of the receptor have different rates of turnover both in the absence and presence of ligand. The biological responses of cells to IL1 stimulation are rapid and occur at low levels of receptor occupancy, whereas receptor mediated endocytosis of IL1 is relatively slow. Internalized IL1 appears to accumulate within cells in a non-degraded form and a proportion of this is associated with a detergent insoluble intracellular fraction, which may reflect transport to the nucleus. In this article, we review our previous findings and discuss the possible biological significance of IL1 internalization and nuclear targeting.
Solari
R
R
Division of Cellular and Molecular Science, Glaxo Group Research, Greenford, Middlesex, U.K.
Smithers
N
N
Kennard
N
N
Ray
K
K
Grenfell
S
S
D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004705:Endocytosis; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D007457:Iodine Radioisotopes; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D007457:Iodine Radioisotopes; D017472:Receptors, Interleukin-1