Phosphatidylinositol 3-kinase translocation to the nucleus is induced by interleukin 1 and prevented by mutation of interleukin 1 receptor in human osteosarcoma Saos-2 cells.
Although interleukin 1 (IL-1) functions have been extensively characterized, the mechanisms by which IL-1 signals are transduced from the plasma membrane to the nucleus are less known. Recent evidence indicates that phosphatidylinositol 3-kinase (PI3-kinase) could be activated by a direct association with the activated IL-1 receptor. In this study we analyzed the effects of IL-1 on the intracellular distribution of PI3-kinase in wild-type Saos-2 human osteosarcoma cells, and in cell clones overexpressing type I IL-1 receptor (IL-1RI). PI3-kinase intracellular distribution displays two distinct patterns. In quiescent cells, PI3-kinase is distributed through the cytoplasm, although a portion is present in the nucleus; following stimulation with IL-1, PI3-kinase is redistributed, increasing in the nuclear compartment. Both immunoblotting and immunofluorescence data indicate that IL-1 causes a rapid and transient translocation of PI3-kinase from the cytoplasm to the nucleus. This phenomenon is prevented by PI3-kinase inhibitors, suggesting that the maintenance of PI3-kinase activity is essential for IL-1-induced translocation. Indeed, in cell clones stably transfected with Y479F receptor mutant, in which the binding of the enzyme to the activated receptor is blocked, IL-1-induced PI3-kinase translocation to the nucleus is completely prevented. These data suggest that PI3-kinase translocation to the nucleus upon IL-1R activation is an early event in IL-1 signaling mechanism, and may be involved in transcriptional activation.
Bavelloni
A
A
Laboratory of Cell Biology and Electron Microscopy, IOR, and Institute of Normal and Pathological Cytomorphology, CNR c/o IOR, Bologna 40136, Italy.
Santi
S
S
Sirri
A
A
Riccio
M
M
Faenza
I
I
Zini
N
N
Cecchi
S
S
Ferri
A
A
Auron
P
P
Maraldi
N M
NM
Marmiroli
S
S
D001483:Base Sequence; D001693:Biological Transport, Active / Q000187:drug effects; D002467:Cell Nucleus / Q000201:enzymology; D003593:Cytoplasm / Q000201:enzymology; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D017472:Receptors, Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured