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Titolo:
The Src-protein tyrosine kinase Lck is required for IL-1-mediated costimulatory signaling in Th2 cells
Autore:
al-Ramadi, BK; Welte, T; Fernandez-Cabezudo, MJ; Galadari, S; Dittel, B; Fu, XY; Bothwell, ALM;
Indirizzi:
United Arab Emirates Univ, Fac Med & Hlth Sci, Dept Med Microbiol, Al Ain,U Arab Emirates United Arab Emirates Univ Al Ain U Arab Emirates Al Ain,U Arab Emirates United Arab Emirates Univ, Fac Med & Hlth Sci, Dept Biochem, Al Ain, U Arab Emirates United Arab Emirates Univ Al Ain U Arab Emirates l Ain, U Arab Emirates Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06510 USA Yale Univ New Haven CT USA 06510 Immunobiol Sect, New Haven, CT 06510 USA Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA Yale Univ New Haven CT USA 06510 ed, Dept Pathol, New Haven, CT 06510 USA
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 12, volume: 167, anno: 2001,
pagine: 6827 - 6833
SICI:
0022-1767(200112)167:12<6827:TSTKLI>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
NF-KAPPA-B; MONOCLONAL-ANTIBODY; IL-2 RECEPTOR; T-CELLS; ACTIVATION; COMPLEX; ALPHA; BETA; PHOSPHORYLATION; INTERLEUKIN-1;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: al-Ramadi, BK United Arab Emirates Univ, Fac Med & Hlth Sci, Dept Med Microbiol, POB 17666, Al Ain, U Arab Emirates United Arab Emirates Univ POB 17666 Al Ain U Arab Emirates
Citazione:
B.K. al-Ramadi et al., "The Src-protein tyrosine kinase Lck is required for IL-1-mediated costimulatory signaling in Th2 cells", J IMMUNOL, 167(12), 2001, pp. 6827-6833

Abstract

Src-protein tyrosine kinases are intimately involved in TCR-initiated signaling in T lymphocytes. One member of this family, Lek, is also involved inCD28-mediated costimulation in Th1 cells. In Th2 lymphocytes, the costimulatory signal can also be provided by the interaction of IL-1 with type I IL-1R (IL-IRI), culminating in the activation of NF-kappaB transcription factors. Proximal steps in the IL-1R pathway, however, remain poorly understood, and there is conflicting evidence as to the importance of tyrosine phosphorylation in IL-1R signaling. We have addressed this issue by examining theability of IL-1 to costimulate the activation of Lek-deficient Th2 cells. Our data demonstrate that, in the absence of Lck, the IL-1 costimulatory pathway is blocked despite the expression of normal levels of IL-1RI. Moreover, the block is associated with a defective degradation of I kappaB-alpha and an incomplete activation of NF-kappaB heterodimeric complexes. Protein expression of NF-kappaB monomers, including p50, p65, and c-Rel, is equivalent in both wild-type and Lck-deficient Th2 cell clones. Finally, we demonstrate that, in normal Th2 cells, stimulation with IL-1 leads to a rapid induction in tyrosine phosphorylation of several substrates including Lek itself. These findings strongly suggest that Lek is required for signaling in the IL-1 costimulatory pathway in Th2 lymphocytes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 00:52:41