Oligomerization of IL-2Ralpha.
Interleukin (IL) 2 receptor subunit alpha (IL-2Ralpha) increases the affinity of the IL-2 receptor complex while hetero-association of IL-2Rbeta and gamma(c) chains initiates a proliferative signal. We show here that IL-2Ralpha is necessary for receptor clustering required for augmentation of IL-2 signalling. Cells expressing chimeras incorporating the extracellular domain of IL-2Ralpha demonstrated IL-2 independent homo-association of the IL-2Ralpha chimera. Singly or co-transfected IL-2Rbeta and gamma(c) chimeras showed no spontaneous or IL-2-inducible oligomerization. Co-transfection of IL-2Ralpha and IL-2Rbeta (+/- gamma(c)) chimeras diminished spontaneous IL-2Ralpha chimera oligomerization and permitted IL-2-inducible hetero-oligomerization of receptor components. Homo-association of IL-2Ralpha was also demonstrated by fluorescence resonance energy transfer (FRET). The spontaneous homo-oligomerization property of IL-2Ralpha required the membrane proximal region of the receptor (exon 6) by deletion analysis; the IL-2 inducible oligomerization property of IL-2Ralpha required the second "sushi" domain (exon 4). This work provides insight into the mechanics of this complex receptor system and to other receptor complexes in the immune system that send signals by clustering receptor subunits.
Eicher
Donald M
DM
Division of Hematology-Oncology, Ireland Cancer Center, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106-4937, USA. dme8@po.cwru.edu
Damjanovich
Sandor
S
Waldmann
Thomas A
TA
D000469:Alkaline Phosphatase / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D005091:Exons; D017930:Genes, Reporter; D006801:Humans; D019169:Jurkat Cells; D016296:Mutagenesis; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D009842:Oligopeptides / Q000096:biosynthesis* / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D013050:Spectrometry, Fluorescence / Q000379:methods; D014157:Transcription Factors / Q000235:genetics
D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D009842:Oligopeptides; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D000469:Alkaline Phosphatase