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Titolo:
Role of MEKK2-MEK5 in the regulation of TNF-alpha gene expression and MEKK2-MKK7 in the activation of c-Jun N-terminal kinase in mast cells
Autore:
Chayama, K; Papst, PJ; Garrington, TP; Pratt, JC; Ishizuka, T; Webb, S; Ganiatsas, S; Zon, LI; Sun, WY; Johnson, GL; Gelfand, EW;
Indirizzi:
Natl Jewish Med & Res Ctr, Dept Pediat, Div Basic Sci, Denver, CO 80206 USA Natl Jewish Med & Res Ctr Denver CO USA 80206 c Sci, Denver, CO 80206 USA Natl Jewish Med & Res Ctr, Program Mol Signal Transduct, Denver, CO 80206 USA Natl Jewish Med & Res Ctr Denver CO USA 80206 sduct, Denver, CO 80206 USA Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA Univ Colorado Denver CO USA 80262 r, Dept Pharmacol, Denver, CO 80262 USA Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA Childrens Hosp Boston MA USA 02115 Hughes Med Inst, Boston, MA 02115 USA Childrens Hosp, Div Hematol, Boston, MA 02115 USA Childrens Hosp Boston MA USA 02115 osp, Div Hematol, Boston, MA 02115 USA
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 8, volume: 98, anno: 2001,
pagine: 4599 - 4604
SICI:
0027-8424(20010410)98:8<4599:ROMITR>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
FC-EPSILON-RI; PROTEIN-KINASES; DIFFERENTIAL ACTIVATION; NH2-TERMINAL KINASE; SIGNALING PATHWAYS; MEK KINASE-2; IN-VIVO; MKK7; JNK; SEK1;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Gelfand, EW Natl Jewish Med & Res Ctr, Dept Pediat, Div Basic Sci, 1400 Jackson St, Denver, CO 80206 USA Natl Jewish Med & Res Ctr 1400 Jackson St Denver CO USA 80206
Citazione:
K. Chayama et al., "Role of MEKK2-MEK5 in the regulation of TNF-alpha gene expression and MEKK2-MKK7 in the activation of c-Jun N-terminal kinase in mast cells", P NAS US, 98(8), 2001, pp. 4599-4604

Abstract

Cross-linking of the high-affinity IgE receptor (Fc epsilon RI) on mast cells with IgE and multivalent antigen triggers mitogen-activated protein (MAP) kinase activation and cytokine gene expression. We report here that MAP kinase kinase 4 (MKK4) gene disruption does not affect either MAP kinase activation or cytokine gene expression in response to cross-linking of Fc epsilon RI in embryonic stem cell-derived mast cells. MKK7 is activated in response to crosslinking of Fc epsilon RI, and this activation is inhibited byMAP/ERK kinase (MEK) kinase 2 (MEKK2) gene disruption. In addition, expression of kinase-inactive MKK7 in the murine mast cell line MC/9 inhibits c-Jun NH2-terminal kinase (JNK) activation in response to cross-linking of Fc epsilon RI, whereas expression of kinase-inactive MKK4 does not affect JNK activation by this stimulus. However, Fc epsilon RI-induced activation of the tumor necrosis factor-alpha (TNF-alpha) gene promoter is not affected byexpression of kinase-inactive MKK7. We describe an alternative pathway by which MEKK2 activates MEK5 and big MAP kinase1/extracellular signal-regulated kinase 5 in addition to MKK7 and JNK, and interruption of this pathway inhibits TNF-alpha promoter activation. These findings suggest that INK activation by antigen cross-linking is dependent on the MEKK2-MKK7 pathway, andcytokine production in mast cells is regulated in part by the signaling complex MEKK2-MEK5-ERK5.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 00:24:30