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
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.