SIGNAL-TRANSDUCTION MEDIATED BY THE RECONSTITUTED IL-2 RECEPTOR - EVIDENCE FOR A CELL-TYPE-SPECIFIC FUNCTION OF IL-2 RECEPTOR BETA-CHAIN

Citation
Y. Minami et al., SIGNAL-TRANSDUCTION MEDIATED BY THE RECONSTITUTED IL-2 RECEPTOR - EVIDENCE FOR A CELL-TYPE-SPECIFIC FUNCTION OF IL-2 RECEPTOR BETA-CHAIN, The Journal of immunology, 152(12), 1994, pp. 5680-5690
Citations number
53
Categorie Soggetti
Immunology
Journal title
The Journal of immunology
ISSN journal
00221767 → ACNP
Volume
152
Issue
12
Year of publication
1994
Pages
5680 - 5690
Database
ISI
SICI code
0022-1767(1994)152:12<5680:SMBTRI>2.0.ZU;2-T
Abstract
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 whi ch the three IL-2R subunits, the alpha-chain (IL-2R alpha), the beta-c hain (IL-2R beta), and the gamma-chain (IL-2R gamma), are constitutive ly 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 fi broblasts 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 I L-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 th ree nuclear proto-oncogenes. On the other hand, our previous studies h ad demonstrated that the high affinity IL-2R bearing the same mutant I L-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, th ese results reveal the underlying complexity of signal transduction am ong different cell types. The inability of the reconstituted high affi nity receptor to mediate the IL-2-induced proliferation of NIH 3T3 fib roblasts suggests that induction of the three nuclear proto-oncogenes and the tyrosine phosphorylation of mitogen-activated protein kinase i n NIH 3T3 fibroblasts are not sufficient to induce cellular proliferat ion.