title: Binding of interleukin 2 to its 75-kDa intermediate affinity receptor is sufficient to activate Na+/H+ exchange.
abstract: High affinity interleukin 2 (IL-2) binding sites are composed of two IL-2-binding molecules: one of 55 kDa, commonly called TaC, and another of 75 kDa. In the absence of the other IL-2-binding molecule, the 55-kDa molecule binds IL-2 with a relatively low affinity and the 75 kDa molecule binds IL-2 with an intermediate affinity. One of the earliest events following interaction of IL-2 with its receptor on the surface of cells is an increase in intracellular pH due to activation of the Na+/H+ antiport. In contrast to IL-2-induced proliferation of human IL-2-sensitive T cells, interaction of IL-2 with a low affinity binding site was sufficient to activate the Na+/H+ antiport. By determining the effect of IL-2 on cytosolic pH in cells that express one of the two IL-2-binding molecules in the absence of the other IL-2-binding molecule, we have demonstrated that interaction of IL-2 with the 75 kDa IL-2-binding molecule is sufficient to activate the Na+/H+ antiport and thus induce cytosolic alkalinization. This indicates that the 75-kDa IL-2-binding molecule, in the absence of the 55-kDa IL-2-binding molecule, forms a functional receptor that can transduce an activation signal across the cell membrane.
authors.affiliation: Oncology Research, Toronto General Hospital, Ontario, Canada.
authors.forename: G B
authors.initials: GB
authors.lastname: Mills
authors.forename: C
authors.initials: C
authors.lastname: May
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007376:Interleukin-2 / Q000378:metabolism*; D051379:Mice; D011522:Protons; D011971:Receptors, Immunologic / Q000378:metabolism*; D015375:Receptors, Interleukin-2; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers
chemical_list: D002352:Carrier Proteins; D007376:Interleukin-2; D011522:Protons; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium