INTERLEUKIN-4 ACTIVATES A SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION (STAT) PROTEIN WHICH INTERACTS WITH AN INTERFERON-GAMMA ACTIVATION SITE-LIKE SEQUENCE UPSTREAM OF THE I-EPSILON EXON IN A HUMAN B-CELL LINE - EVIDENCE FOR THE INVOLVEMENT OF JANUS-KINASE-3 AND INTERLEUKIN-4 STAT

被引:55
作者
FENGHAO, X
SAXON, A
NGUYEN, A
KE, Z
DIAZSANCHEZ, D
NEL, A
机构
[1] UNIV CALIF LOS ANGELES, CTR HLTH SCI 52175,SCH MED,DEPT MED, DIV CLIN IMMUNOL & ALLERGY, LOS ANGELES, CA 90024 USA
[2] UNIV CALIF LOS ANGELES, SCH MED, INST MOLEC BIOL, LOS ANGELES, CA 90024 USA
[3] UNIV CALIF LOS ANGELES, SCH MED, JONSSON COMPREHENS CANC CTR, LOS ANGELES, CA 90024 USA
关键词
INTERLEUKIN-4-INDUCED NUCLEAR-ACTIVATING FACTOR; GERMLINE; IMMUNOGLOBULIN E; TRANSCRIPTION; SIGNALING;
D O I
10.1172/JCI118138
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Germ line C-epsilon transcripts can be induced by IL-4 in the human B cell line, BL-2. Utilizing a IFN-gamma activation site-like DNA sequence element located upstream of the I-epsilon exon, we demonstrated by gel mobility shift assays that IL-4 induced a binding activity in the cytosol and nucleus of BL-2 cells, This factor was designated IL-4 NAF (IL-4-induced nuclear-activating factors) and was identified as a tyrosine phosphoprotein, which translocates from the cytosol to the nucleus upon IL-4 treatment, Because these are the characteristics of a signal transducer and activator of transcription (Stat) protein, we determined whether antibodies to Stat proteins will interfere with gel mobility shift and found that antibodies to IL-4 Stat, also known as Stat6, but not antibodies to other Stat proteins, interfere with the formation of the IL-4 NAF complex, Congruous with the involvement of a Stat protein, IL-4 induced robust Janus kinase 3 (JAK3) activity in BL-2 cells, Cotransfection of JAK3 with IL-4 Stat into COS-7 cells produced an intracellular activity which bound the same IFN-gamma activation site-like sequence and comigrated with IL-4 NAP in electrophoretic mobility shift assay. These results show that IL-4 NAF is IL-4 Stat, which is activated by JAK3 in response to IL-4 receptor engagement.
引用
收藏
页码:907 / 914
页数:8
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