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Titolo:
Knock-in mutation of the distal four tyrosines of linker for activation ofT cells blocks murine T cell development
Autore:
Sommers, CL; Menon, RK; Grinberg, A; Zhang, WG; Samelson, LE; Love, PE;
Indirizzi:
NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA NCI Bethesda MDUSA 20892 lar & Mol Biol Lab, NIH, Bethesda, MD 20892 USA NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA NICHHD Bethesda MD USA 20892 ian Genes & Dev, NIH, Bethesda, MD 20892 USA Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA Duke Univ Durham NC USA 27710 Med Ctr, Dept Immunol, Durham, NC 27710 USA
Titolo Testata:
JOURNAL OF EXPERIMENTAL MEDICINE
fascicolo: 2, volume: 194, anno: 2001,
pagine: 135 - 142
SICI:
0022-1007(20010716)194:2<135:KMOTDF>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
SIGNALING PATHWAYS; LAT; RECEPTOR; MICE; TCR; CD3-EPSILON; ASSOCIATION; COMPLEXES; SURFACE; PROTEIN;
Keywords:
thymocyte; development; signal transduction; adapter; gene targeting;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Sommers, CL NCI, Cellular & Mol Biol Lab, NIH, Bldg 37,Rm 1E24,37 Convent Dr, Bethesda, MD 20892 USA NCI Bldg 37,Rm 1E24,37 Convent Dr Bethesda MD USA 20892 92 USA
Citazione:
C.L. Sommers et al., "Knock-in mutation of the distal four tyrosines of linker for activation ofT cells blocks murine T cell development", J EXP MED, 194(2), 2001, pp. 135-142

Abstract

The integral membrane adapter protein linker for activation of T cells (LAT) performs a critical function in T cell antigen receptor (TCR) signal transduction by coupling the TCR to downstream signaling pathways. After TCR engagement, LAT is tyrosine phosphorylated by ZAP-70 creating docking sites for multiple src homology 2-containing effector proteins. In the Jurkat T cell line, the distal four tyrosines of LAT bind PLC gamma -1, Grb2, and Gads. Mutation of these four tyrosine residues to phenylalanine (4YF) blocked TCR-mediated calcium mobilization, Erk activation, and nuclear factor (NF)-AT activation. In this study, we examined whether these four tyrosine residues were essential for T cell development by generating LAT "knock-in" mutant mice that express the;4YF mutant protein under the control of endogenousLAT regulatory sequences. Significantly, the phenotype of 4YF knock-in mice was identical to LAT(-/-) (null) mice; thymocyte: development was arrested at the immature CB4(-)CD8(-) stage and no mature T cells were present. Knock-in mice expressing wild-type LAT protein, generated by a similar strategy, displayed a normal T cell developmental profile. These results demonstrate that the distal four tyrosine residues of LAT are essential for preTCR signaling and T cell development in vivo.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/11/20 alle ore 22:44:09