The Integrity of the Conserved 'WS Motif' Common to IL-2 and Other Cytokine Receptors is Essential for Ligand Binding and Signal Transduction

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1991 Nov 1

PMID 1915291

Citations 21

Authors

T Miyazaki

M Maruyama

G Yamada

M Hatakeyama

T Taniguchi

Affiliations

Soon will be listed here.

Abstract

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.

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References

Barber E, Dasgupta J, Schlossman S, Trevillyan J, Rudd C . The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex. Proc Natl Acad Sci U S A. 1989; 86(9):3277-81. PMC: 287114. DOI: 10.1073/pnas.86.9.3277. View

Takaki S, Tominaga A, Hitoshi Y, Mita S, Sonoda E, Yamaguchi N . Molecular cloning and expression of the murine interleukin-5 receptor. EMBO J. 1990; 9(13):4367-74. PMC: 552225. DOI: 10.1002/j.1460-2075.1990.tb07886.x. View

Rao A, Howard O, Ng S, WHITEHEAD A, Colten H, Sodetz J . Complementary DNA and derived amino acid sequence of the alpha subunit of human complement protein C8: evidence for the existence of a separate alpha subunit messenger RNA. Biochemistry. 1987; 26(12):3556-64. DOI: 10.1021/bi00386a046. View

Garvin A, Pawar S, Marth J, Perlmutter R . Structure of the murine lck gene and its rearrangement in a murine lymphoma cell line. Mol Cell Biol. 1988; 8(8):3058-64. PMC: 363532. DOI: 10.1128/mcb.8.8.3058-3064.1988. View

Siegel J, Sharon M, Smith P, Leonard W . The IL-2 receptor beta chain (p70): role in mediating signals for LAK, NK, and proliferative activities. Science. 1987; 238(4823):75-8. DOI: 10.1126/science.3116668. View

Sharon M, Klausner R, Cullen B, Chizzonite R, Leonard W . Novel interleukin-2 receptor subunit detected by cross-linking under high-affinity conditions. Science. 1986; 234(4778):859-63. DOI: 10.1126/science.3095922. View

Tsudo M, Kozak R, Goldman C, Waldmann T . Demonstration of a non-Tac peptide that binds interleukin 2: a potential participant in a multichain interleukin 2 receptor complex. Proc Natl Acad Sci U S A. 1986; 83(24):9694-8. PMC: 387207. DOI: 10.1073/pnas.83.24.9694. View

Hatakeyama M, Minamoto S, Taniguchi T . Intracytoplasmic phosphorylation sites of Tac antigen (p55) are not essential for the conformation, function, and regulation of the human interleukin 2 receptor. Proc Natl Acad Sci U S A. 1986; 83(24):9650-4. PMC: 387198. DOI: 10.1073/pnas.83.24.9650. View

Teshigawara K, Wang H, Kato K, Smith K . Interleukin 2 high-affinity receptor expression requires two distinct binding proteins. J Exp Med. 1987; 165(1):223-38. PMC: 2188268. DOI: 10.1084/jem.165.1.223. View

10.

Tsudo M, Goldman C, Bongiovanni K, Chan W, Winton E, Yagita M . The p75 peptide is the receptor for interleukin 2 expressed on large granular lymphocytes and is responsible for the interleukin 2 activation of these cells. Proc Natl Acad Sci U S A. 1987; 84(15):5394-8. PMC: 298862. DOI: 10.1073/pnas.84.15.5394. View

11.

Dukovich M, Wano Y, Le Thi Bich Thuy , Katz P, Cullen B, Kehrl J . A second human interleukin-2 binding protein that may be a component of high-affinity interleukin-2 receptors. Nature. 1987; 327(6122):518-22. DOI: 10.1038/327518a0. View

12.

Tsudo M, Kitamura F, Miyasaka M . Characterization of the interleukin 2 receptor beta chain using three distinct monoclonal antibodies. Proc Natl Acad Sci U S A. 1989; 86(6):1982-6. PMC: 286829. DOI: 10.1073/pnas.86.6.1982. View

13.

Gearing D, King J, Gough N, Nicola N . Expression cloning of a receptor for human granulocyte-macrophage colony-stimulating factor. EMBO J. 1989; 8(12):3667-76. PMC: 402049. DOI: 10.1002/j.1460-2075.1989.tb08541.x. View

14.

DAndrea A, Lodish H, Wong G . Expression cloning of the murine erythropoietin receptor. Cell. 1989; 57(2):277-85. DOI: 10.1016/0092-8674(89)90965-3. View

15.

Hatakeyama M, Mori H, Doi T, Taniguchi T . A restricted cytoplasmic region of IL-2 receptor beta chain is essential for growth signal transduction but not for ligand binding and internalization. Cell. 1989; 59(5):837-45. DOI: 10.1016/0092-8674(89)90607-7. View

16.

Hatakeyama M, Tsudo M, Minamoto S, Kono T, Doi T, Miyata T . Interleukin-2 receptor beta chain gene: generation of three receptor forms by cloned human alpha and beta chain cDNA's. Science. 1989; 244(4904):551-6. DOI: 10.1126/science.2785715. View

17.

Cosman D, Cerretti D, Larsen A, Park L, March C, Dower S . Cloning, sequence and expression of human interleukin-2 receptor. Nature. 1984; 312(5996):768-71. DOI: 10.1038/312768a0. View

18.

Discipio R, Gehring M, Podack E, Kan C, Hugli T, Fey G . Nucleotide sequence of cDNA and derived amino acid sequence of human complement component C9. Proc Natl Acad Sci U S A. 1984; 81(23):7298-302. PMC: 392133. DOI: 10.1073/pnas.81.23.7298. View

19.

Takeshita T, Asao H, Suzuki J, Sugamura K . An associated molecule, p64, with high-affinity interleukin 2 receptor. Int Immunol. 1990; 2(5):477-80. DOI: 10.1093/intimm/2.5.477. View

20.

Fukunaga R, SOKAWA Y, Nagata S . Constitutive production of human interferons by mouse cells with bovine papillomavirus as a vector. Proc Natl Acad Sci U S A. 1984; 81(16):5086-90. PMC: 391642. DOI: 10.1073/pnas.81.16.5086. View