The integrity of the conserved 'WS motif' common to IL-2 and other cytokine receptors is essential for ligand binding and signal transduction.
Recent studies have identified a new family of cytokine receptors, which is primarily characterized by the conservation of periodically interspersed four cysteine residues and the W-S-X-W-S sequence ('WS motif') within the extracellular domain. However, the role of such conserved structures still remains elusive, in particular that of the WS motif. Interleukin-2 (IL-2) is known to play a critical role in the clonal expansion of antigen-stimulated T lymphocytes, and the IL-2 signal is delivered by one of the receptor components, the IL-2 receptor beta (IL-2R beta) chain. The IL-2R beta chain, unlike the IL-2R alpha chain, belongs to this receptor family. In the present study, we analyzed the function of the WS motif of IL-2R beta (Trp194-Ser195-Pro196-Trp197-Ser198) with the use of site-directed mutagenesis. Our results indicate the critical role of the two Trp residues in the proper folding of the IL-2R beta extracellular domain and point to the general functional importance of the WS motif in the new cytokine receptor family.
Institute for Molecular and Cellular Biology, Osaka University, Japan.
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T
Miyazaki
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M
Maruyama
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G
Yamada
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Hatakeyama
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Taniguchi
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010957:Plasmids; D011233:Precipitin Tests; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D015398:Signal Transduction; D014162:Transfection
D016207:Cytokines; D008024:Ligands; D015375:Receptors, Interleukin-2; D004247:DNA