The 75,000-dalton interleukin-2 receptor transmits a signal for the activation of a tyrosine protein kinase.
The high-affinity receptor for interleukin-2 (IL-2) is composed of two distinct subunits with molecular weights of 55,000 and 75,000 (p55 and p75). While the presence of the high-affinity receptor requires the simultaneous expression of p55 and p75, these subunits can also be expressed independently, resulting in IL-2 receptors with low and intermediate affinities, respectively. IL-2 can induce proliferation in cells expressing either the intermediate affinity p75 receptor or the p55.p75 high-affinity complex, suggesting that p75 is responsible for signal transduction. We have previously shown that signal transduction by the high-affinity IL-2 receptor involves the activation of a tyrosine protein kinase. In order to evaluate the role of p75 in the activation of this kinase we assessed the ability of IL-2 to induce the activation of a tyrosine protein kinase in the human leukemic cell lines Hut 78 and YT. These cells express p75 as the predominant IL-2 receptor. IL-2-dependent tyrosine phosphorylation was observed in both cell lines and the concentrations of IL-2 needed to stimulate this phosphorylation were similar to that required for binding to the p75 receptor. Antibodies that inhibit binding of IL-2 to p55 had no effect on the IL-2-induced tyrosine phosphorylations in YT cells, while antibodies that block the binding of IL-2 to p75 completely inhibited the phosphorylations. These results demonstrate that the signaling capacity for the IL-2-induced tyrosine phosphorylation resides in the p75 receptor.
Saltzman
E M
EM
Department of Pharmacology and Cancer Center, University of Rochester Medical Center, New York 14642.
Luhowskyj
S M
SM
Casnellie
J E
JE
D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D004789:Enzyme Activation; D016650:Fluorescein-5-isothiocyanate; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D015398:Signal Transduction; D013861:Thiocyanates
D005452:Fluoresceins; D005456:Fluorescent Dyes; D015375:Receptors, Interleukin-2; D013861:Thiocyanates; D011505:Protein-Tyrosine Kinases; D016650:Fluorescein-5-isothiocyanate