MEKK1 Binds HECT E3 Ligase Itch by Its Amino-Terminal RING Motif to Regulate Th2 Cytokine Gene Expression

被引：22

作者：

Enzler, Thomas ^{[1
]}

Chang, Xing ^{[2
,3
]}

Facchinetti, Valeria ^{[4
]}

Melino, Gerry ^{[5
]}

Karin, Michael ^{[6
]}

Su, Bing ^{[2
,3
]}

Gallagher, Ewen ^{[7
]}

机构：

[1] Stanford Univ, Sch Med, Stanford, CA 94305 USA

[2] Yale Univ, Sch Med, Dept Immunol, New Haven, CT 06519 USA

[3] Yale Univ, Sch Med, Vasc Biol & Therapeut Program, New Haven, CT 06519 USA

[4] Univ Texas Houston, MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA

[5] Univ Roma Tor Vergata, Dept Expt Med & Biochem Sci, Ist Dermopat Immacolata, Carattere Sci Biochem Lab,Ist Ricovero & Cura, Rome, Italy

[6] Univ Calif San Diego, Dept Pharmacol, Sch Med, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA

[7] Univ London Imperial Coll Sci Technol & Med, Dept Immunol, London, England

来源：

JOURNAL OF IMMUNOLOGY | 2009年 / 183卷 / 06期

关键词：

SIGNALING PATHWAYS; KINASE; JNK; PHOSPHORYLATION; ACTIVATION; DIFFERENTIATION; ANTIGEN; CELLS; TAK1; MICE;

D O I：

10.4049/jimmunol.0803412

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

MEKK1-dependent signaling regulates HECT E3 ligase Itch, resulting in elevated catalytic activity. After TCR costimulation, MEKK1 predominantly induces JNK1 activation, whereas the related kinase MEKK2 regulates ERK5 activation. MEKK1 becomes phosphorylated on multiple sites and polyubiquitinated following TCR costimulation. E3 ligase Itch is recruited to activated MEKK1, but not MEKK2, and this novel scaffolding interaction is dependent on MEKK1 Thr(1381) phosphorylation within the kinase domain and an intact MEKK1 RING finger motif. MEKK1 phosphorylation on Thr(1381) is observed during Th2 differentiation, but not under Th1 differentiation. Both Itch and the MEKK1 kinase domain are important for 114 and 116 cytokine gene expression under Th2 conditions. The Journal of Immunology, 2009, 183: 3831-3838.

引用

页码：3831 / 3838

页数：8

共 34 条

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