Interleukin-12 induces tyrosine phosphorylation of an 85-kDa protein associated with the interleukin-12 receptor beta 1 subunit.
Interleukin-12 (IL12) is a heterodimeric cytokine composed of p35 and p40 subunits and having multiple immunomodulatory effects on T cells as well as on natural killer cells. Two subunits, beta 1 and beta 2, consisting of the functional IL12 receptor complex, have been recently identified as members of the hemopoietin receptor superfamily, bearing strong homology to gp130. In the present study, we attempted to further characterize the biochemical nature of the IL12 receptor complex and to delineate IL12-triggered signal transduction pathways. To this end, we established a Jurkat transfectant (JIL12R beta 1t) highly expressing the recombinant human IL12 receptor beta 1 subunit. Using this transfectant, we identified an 85-kDa protein (p85) which is associated with the beta 1 subunit and appears to be a cell surface protein, but is distinct from the beta 2 subunit (130 kDa). p85 was also detected in PHA-activated T cells. Importantly, p85 was rapidly tyrosine phosphorylated upon stimulation of both JIL12R beta 1t cells and PHA-activated T cells with IL12. These results suggest that p85 is a component of the IL12 receptor complex and may play a significant role in mediating IL12-dependent signals.
Kawashima
T
T
Department of Clinical Immunology, University of Tokyo, Japan. kawasaki@ims.u-tokyo.ac.jp
Kawasaki
H
H
Kitamura
T
T
Nojima
Y
Y
Morimoto
C
C
D000818:Animals; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D053707:Receptors, Interleukin-12; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism*
D008565:Membrane Proteins; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D011994:Recombinant Proteins; D018664:Interleukin-12; D014443:Tyrosine