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Titolo:
IL-2R beta agonist p1-30 acts in synergy with IL-2, IL-4, IL-9, and IL-15:Biological and molecular effects
Autore:
Eckenberg, R; Moreau, JL; Melnyk, O; Theze, J;
Indirizzi:
Inst Pasteur, Dept Immunol, Unite Immunogenet Cellulaire, F-75724 Paris 15, France Inst Pasteur Paris France 15 ogenet Cellulaire, F-75724 Paris 15, France Inst Pasteur, F-59019 Lille, France Inst Pasteur Lille France F-59019Inst Pasteur, F-59019 Lille, France Inst Biol, Lille, France Inst Biol Lille FranceInst Biol, Lille, France
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 8, volume: 165, anno: 2000,
pagine: 4312 - 4318
SICI:
0022-1767(20001015)165:8<4312:IBAPAI>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTOR-BETA-CHAIN; HUMAN INTERLEUKIN-2 RECEPTOR; T-CELL PROLIFERATION; GAMMA-CHAIN; ALPHA-CHAIN; CYTOPLASMIC DOMAINS; SIGNALING PATHWAYS; CYTOKINE RECEPTORS; HIGH-AFFINITY; C-JUN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
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., "IL-2R beta agonist p1-30 acts in synergy with IL-2, IL-4, IL-9, and IL-15:Biological and molecular effects", J IMMUNOL, 165(8), 2000, pp. 4312-4318

Abstract

From the sequence of human IL-2 we have recently characterized a peptide (p1-30), which is the first IL-2 mimetic described. P1-30 covers the entire alpha helix A of IL-2 and spontaneously folds into a alpha helical homotetramer mimicking the quaternary structure of a hemopoietin, This neocytokine interacts with a previously undescribed dimeric form of the human IL-2 receptor beta-chain likely to form the p1-30 receptor (p1-30R), P1-30 acts as aspecific IL-2R beta agonist, selectively inducing activation of CDS and NKlymphocytes, From human PBMC we have also shown that p1-30 induces the activation of lymphokine-activated killer cells and the production of IFN-gamma. Here we demonstrate the ability of p1-30 to act in synergy with IL-2, -4, -9, and -15, These synergistic effects mere analyzed at the functional level by using TS1 beta, a murine T cell line endogenously expressing the common cytokine gamma gene and transfected with the human IL-2R beta gene. At the receptor level, we show that expression of human IL-2R beta is absolutely required to obtain synergistic effects, whereas IL-2R alpha specificallyimpedes the synergistic effects obtained with IL-2, The results suggest that overexpression of IL-2R alpha inhibits p1-30R formation in the presence of IL-2, Finally, concerning the molecular effects, although p1-30 alone induces the antiapoptotic molecule bcl-2, we show that it does not influence mRNA expression of c-myc, c-jun, and c-fos oncogenes, In contrast, p1-30 enhances IL-2-driven expression of these oncogenes, Our data suggest that p1-30R (IL-2R beta)(2) and intermediate affinity IL-2R (IL-2R beta gamma), when simultaneously expressed at the cell surface, may induce complementary signal transduction pathways and act in synergy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 10:00:00