Leptin receptor (OB-R) signaling - Cytoplasmic domain mutational analysis and evidence for receptor homo-oligomerization

被引:249
作者
White, DW
Kuropatwinski, KK
Devos, R
Baumann, H
Tartaglia, LA
机构
[1] ROSWELL PK CANC INST,DEPT MOL & CELLULAR BIOL,BUFFALO,NY 14263
[2] MILLENNIUM PHARMACEUT,CAMBRIDGE,MA 02215
[3] ROCHE RES GENT,B-9000 GHENT,BELGIUM
关键词
D O I
10.1074/jbc.272.7.4065
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The leptin receptor (OB-R) mediates the weight regulatory effects of the adipocyte secreted hormone leptin (OB), Previously we have shown that the long form of OB-R, expressed predominantly in the hypothalamus, can mediate ligand-induced activation of signal transducer and activator of transcription factors 1, 3, and 5 and stimulate transcription via interleukin-6 and hematopoietin receptor responsive gene elements. Here we report that deletion and tyrosine substitution mutagenesis of OB-R identifies two distinct regions of the intracellular domain important for signaling. In addition, granulocyte-colony stimulatory factor receptor/OB-R and OB-R/granulocyte-colony stimulatory factor receptor chimeras are signaling competent and provide evidence that aggregation of two OB-R intracellular domains is sufficient for ligand-induced receptor activation. However, signaling by full-length OB-R appears to be relatively resistant to dominant negative repression by signaling-incompetent OB-R, suggesting that mechanisms exist to permit signaling by the long form of OB-R even in the pretence of excess naturally occurring short form of OB-R.
引用
收藏
页码:4065 / 4071
页数:7
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