Signal transduction mediated by the reconstituted IL-2 receptor. Evidence for a cell type-specific function of IL-2 receptor beta-chain.
The binding of IL-2 to its specific receptor (IL-2R) triggers various cellular events including the induction of nuclear proto-oncogenes (c-fos, c-jun and c-myc genes) and the proliferation of hemopoietic cells. In the present study, we have established NIH 3T3 fibroblasts in which the three IL-2R subunits, the alpha-chain (IL-2R alpha), the beta-chain (IL-2R beta), and the gamma-chain (IL-2R gamma), are constitutively expressed. The resulting cell lines express high affinity IL-2R on their cell surface at levels comparable with those of IL-2-responsive lymphoid cells. We observed that the high affinity IL-2R in NIH 3T3 fibroblasts can mediate the IL-2-stimulated tyrosine phosphorylation of p42/p44 (mitogen-activated protein kinase) and the induction of the c-fos, c-jun and c-myc genes. In NIH 3T3 fibroblasts the high affinity IL-2R bearing a deletion of a region rich in acidic amino acids (the "acidic" region) in the IL-2R beta-chain failed to induce the tyrosine phosphorylation of MAP kinase as well as the expression of the all three nuclear proto-oncogenes. On the other hand, our previous studies had demonstrated that the high affinity IL-2R bearing the same mutant IL-2R beta-chain retained the ability to induce c-myc gene in response to IL-2 in a murine IL-3-dependent pro-B cell line, BAF/B03. Hence, these results reveal the underlying complexity of signal transduction among different cell types. The inability of the reconstituted high affinity receptor to mediate the IL-2-induced proliferation of NIH 3T3 fibroblasts suggests that induction of the three nuclear proto-oncogenes and the tyrosine phosphorylation of mitogen-activated protein kinase in NIH 3T3 fibroblasts are not sufficient to induce cellular proliferation.
Minami
Y
Y
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Oishi
I
I
Liu
Z J
ZJ
Nakagawa
S
S
Miyazaki
T
T
Taniguchi
T
T
D016475:3T3 Cells / Q000187:drug effects / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D015870:Gene Expression; D016762:Genes, fos; D016758:Genes, jun; D016259:Genes, myc; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D051379:Mice; D010766:Phosphorylation; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D014443:Tyrosine / Q000378:metabolism
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D014443:Tyrosine