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Titolo:
The first alpha helix of interleukin (IL)-2 folds as a homotetramer, acts as an agonist of the IL-2 receptor beta chain, and induces lymphokine-activated killer cells
Autore:
Eckenberg, R; Rose, T; Moreau, JL; Weil, R; Gesbert, F; Dubois, S; Tello, D; Bossus, M; Gras, H; Tartar, A; Bertoglio, J; Chouaib, S; Goldberg, M; Jacques, Y; Alzari, PM; Theze, J;
Indirizzi:
Inst Pasteur, Unite Immunogenet Cellulaire, F-75015 Paris, France Inst Pasteur Paris France F-75015 enet Cellulaire, F-75015 Paris, France Inst Pasteur, Unite Biochim Cellulaire, F-75015 Paris, France Inst Pasteur Paris France F-75015 chim Cellulaire, F-75015 Paris, France Inst Pasteur, Unite Biol Mol Express Gen, F-75015 Paris, France Inst Pasteur Paris France F-75015 Mol Express Gen, F-75015 Paris, France Inst Pasteur, Unite Biochim Struct, F-75015 Paris, France Inst Pasteur Paris France F-75015 Biochim Struct, F-75015 Paris, France INSERM, U461, F-92296 Chatenay Malabry, France INSERM Chatenay Malabry France F-92296 F-92296 Chatenay Malabry, France INSERM, U463, F-44000 Nantes, France INSERM Nantes France F-44000INSERM, U463, F-44000 Nantes, France Inst Pasteur, F-59000 Lille, France Inst Pasteur Lille France F-59000Inst Pasteur, F-59000 Lille, France INSERM, U487, F-94805 Villejuif, France INSERM Villejuif France F-94805INSERM, U487, F-94805 Villejuif, France
Titolo Testata:
JOURNAL OF EXPERIMENTAL MEDICINE
fascicolo: 3, volume: 191, anno: 2000,
pagine: 529 - 539
SICI:
0022-1007(20000207)191:3<529:TFAHOI>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
GAMMA-CHAIN; EXPRESSION; BINDING; PROTEIN; IDENTIFICATION; CYTOKINE; DOMAINS; SUBUNIT; CLONING; ERYTHROPOIETIN;
Keywords:
interleukin 2 mimetic; synthetic hemopoietin; dimeric interleukin 2 receptor beta chain; signal transduction; natural killer cells;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Theze, J Inst Pasteur, Dept Immunol, Unite Immunogenet Cellulaire, 25 & 28Rue Dr Roux, F-75724 Paris 15, France Inst Pasteur 25 & 28 Rue Dr Roux Paris France 15 aris 15, France
Citazione:
R. Eckenberg et al., "The first alpha helix of interleukin (IL)-2 folds as a homotetramer, acts as an agonist of the IL-2 receptor beta chain, and induces lymphokine-activated killer cells", J EXP MED, 191(3), 2000, pp. 529-539

Abstract

Interleukin (IL)-2 interacts with two types of functional receptors (IL-2Ralpha beta gamma and IL-2R beta gamma) and acts on a broad range of targetcells involved in inflammatory reactions and immune responses. For the first time, we show that a chemically synthesized fragment of the IL-2 sequence can fold into a molecule mimicking the quaternary structure of a hemopoietin. Indeed, peptide p1-30 (containing amino acids 1-30, coveting the entire alpha helix A of IL-2) spontaneously folds into an alpha-helical homotetramer and stimulates the growth of T cell lines expressing human IL-2R beta,whereas shorter versions of the peptide lack helical structure and are inactive. We also demonstrate that this neocytokine interacts with a previously undescribed dimeric form of IL-2R beta. In agreement with its binding to IL-2R beta, p1-30 activates Shc and p56(lck) but unlike IL-2, fails to activate Janus kinase (Jak)1, Jak3, and signal transducer and activator of transcription 5 (STAT5). Unexpectedly, we also show that p1-30 activates Tyk2, thus suggesting that IL-2R beta may bind to different Jaks depending on itsoligomerization. At the cellular level, p1-30 induces lymphokine-activatedkiller (LAK) cells and preferentially activates CD8(low) lymphocytes and natural killer cells, which constitutively express IL-2R beta. A significantinterferon gamma production is also detected after p1-30 stimulation. A mutant form of p1-30 (Asp20-->Lys), which is likely unable to induce vascularleak syndrome, remains capable of generating LAK cells, like the original p1-30 peptide. Altogether, our data suggest that p1-30 has therapeutic potential.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/20 alle ore 09:45:15