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Titolo:
Roles of phosphatidylinositol 3-kinase in interferon-gamma-dependent phosphorylation of STAT1 on serine 727 and activation of gene expression
Autore:
Nguyen, H; Ramana, CV; Bayes, J; Stark, GR;
Indirizzi:
Cleveland Clin Fdn, Dept Mol Biol, Lerner Res Inst, Cleveland, OH 44195 USA Cleveland Clin Fdn Cleveland OH USA 44195 s Inst, Cleveland, OH 44195 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 36, volume: 276, anno: 2001,
pagine: 33361 - 33368
SICI:
0021-9258(20010907)276:36<33361:ROP3II>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE-B; EPIDERMAL GROWTH-FACTOR; GLYCOGEN-SYNTHASE KINASE-3; CELL ANTIGEN RECEPTOR; C-CBL PROTOONCOGENE; NF-KAPPA-B; TYROSINE PHOSPHORYLATION; IFN-GAMMA; TRANSCRIPTION FACTOR; SIGNALING PATHWAY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
73
Recensione:
Indirizzi per estratti:
Indirizzo: Stark, GR Cleveland Clin Fdn, Dept Mol Biol, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA Cleveland Clin Fdn 9500 Euclid Ave Cleveland OH USA 44195 95 USA
Citazione:
H. Nguyen et al., "Roles of phosphatidylinositol 3-kinase in interferon-gamma-dependent phosphorylation of STAT1 on serine 727 and activation of gene expression", J BIOL CHEM, 276(36), 2001, pp. 33361-33368

Abstract

STAT1 must be phosphorylated on serine 727 to be fully active in transcription. We show that phosphatidylinositol 3-kinase (PI3K) and its effector kinase Akt play an important role in the serine phosphorylation of STAT1 and in the activation of gene expression in response to interferon-gamma (IFN gamma). IFN gamma activates PI3K as well as Akt in a variety of cell lines. Specific inhibition of PI3K abrogates IFN gamma -induced, but not interleukin-1- or tumor necrosis factor-a-induced, phosphorylation of STAT1. on serine and reduces STAT1-dependent transcription and gene expression by similarto7-fold. Constitutively active forms of P13K or Akt activate and their dominant-negative derivatives inhibit STAT1-driven transactivation in response to IFN gamma. In addition to PI3K and Akt, JAK1, JAK2, and the tyrosine 440 STAT1 docking residue of IFNGR1 are required for STAT1 to be phospho. rylated on serine. Taken together, these results suggest that the following events lead to the activation of STAT1 upon IFN gamma stimulation: 1) P13K and Akt are activated by the occupied receptor and Tyr-440 is phosphorylatedby the activated JAKs; 2) STAT1 docks to Tyr-440; and 3) Tyr-701 is phosphorylated by the JAKs and Ser-727 is phosphorylated by a kinase downstream of Akt.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 01:46:40