THE CYTOPLASMIC DOMAIN OF THE INTERLEUKIN-2 RECEPTOR-BETA CHAIN CONTAINS BOTH UNIQUE AND FUNCTIONALLY REDUNDANT SIGNAL-TRANSDUCTION ELEMENTS

Binding of interleukin-2 (IL-2) to the IL-2 receptor (IL-2R) triggers a series of intracellular events culminating in lymphocyte proliferati on and differentiation. A novel transient assay of signal transduction leading to proliferation is now described which allows the rapid func tional assessment of wild type and mutant receptors, including the IL- 2R and other members of the cytokine receptor superfamily. This assay has been used to define domains and specific residues within the IL-2R beta intracellular region that contribute to growth signal transducti on. In these studies, internal deletion of either the conserved ''Box 1'' or ''Box 2'' proximal cytokine receptor homology segments signific antly impaired receptor function. Similarly, mutation of specific key residues within or between Box 1 and Box 2, or deletion of the C-termi nal 94 residues of the IL-2R beta chain, impaired growth signaling. In contrast, either replacement of the transmembrane domain with that of the CD4 molecule or internal deletion of the 119 amino acids immediat ely downstream of Box 2 had no impact on growth signaling competence. These studies thus further define the functional architecture of the i ntracellular region of IL-2R beta, and reveal specific receptor domain s that are dispensable, unique, or functionally redundant.