Expression of an active p110 catalytic subunit of phosphatidylinositol 3-kinase alters the proliferative capacity of interleukin-2 receptor signals.
Activation of phosphatidylinositol 3-kinase (PI3K) is an early and essential step in interleukin-2 receptor (IL-2R) signalling, and plays an important role in regulating both cell survival and cellular proliferation. In the present study, we utilized Baf-B03 cells expressing mutated IL-2R to examine the contribution of PI3K to proliferative capacity. In this model IL-2-mediated induction of the downstream PI3K-dependent signalling molecule p70 S6 kinase was detected, but there was no proliferative response. Increasing the level of PI3K activity by transfection of an active form of the catalytic subunit, p110*, enabled the proliferative capacity of the mutated receptor. Whereas, in cells without p110*, IL-2 lacked the capacity to induce c-myc and to overcome an S-phase checkpoint, S-phase transition was restored by transfection of p110*, and this was accompanied by an increase in the c-myc response. Despite the presence of p110*, activity cells still required IL-2R-derived signals for proliferation, and IL-2Rbeta truncated at amino acid 350 were sufficient to provide this signalling activity. The data support a model in which the level of available PI3K can determine the cellular response to IL-2.
Gala
Salvador
S
Institute for Immunology and Allergy Research, Westmead Millennium Institute, Sydney, Australia.
Schibeci
Stephen Donald
SD
Marreiros
Alexandra
A
Calvo
Victor
V
Merida
Isabel
I
Williamson
Peter
P
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation; D004789:Enzyme Activation; D016259:Genes, myc; D051379:Mice; D008807:Mice, Inbred BALB C; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
D018797:Cell Cycle Proteins; D015375:Receptors, Interleukin-2; D019869:Phosphatidylinositol 3-Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa