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 proliferation and differentiation. A novel transient assay of signal transduction leading to proliferation is now described which allows the rapid functional 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 transduction. In these studies, internal deletion of either the conserved "Box 1" or "Box 2" proximal cytokine receptor homology segments significantly impaired receptor function. Similarly, mutation of specific key residues within or between Box 1 and Box 2, or deletion of the C-terminal 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 immediately downstream of Box 2 had no impact on growth signaling competence. These studies thus further define the functional architecture of the intracellular region of IL-2R beta, and reveal specific receptor domains that are dispensable, unique, or functionally redundant.
Goldsmith
M A
MA
Gladstone Institute of Virology and Immunology, San Francisco Hospital, California 94141-9100.
Xu
W
W
Amaral
M C
MC
Kuczek
E S
ES
Greene
W C
WC
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002522:Chlorocebus aethiops; D017124:Conserved Sequence; D003432:Cross-Linking Reagents; D007376:Interleukin-2 / Q000378:metabolism* / Q000494:pharmacology*; D007668:Kidney; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction; D013388:Succinimides; D014162:Transfection
D003432:Cross-Linking Reagents; D007376:Interleukin-2; D046911:Macromolecular Substances; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D013388:Succinimides; C019358:disuccinimidyl suberate