PTP1D is a positive regulator of the prolactin signal leading to beta-casein promoter activation

被引:126
作者
Ali, S
Chen, ZJ
Lebrun, JJ
Vogel, W
Kharitonenkov, A
Kelly, PA
Ullrich, A
机构
[1] MAX PLANCK INST BIOCHEM, DEPT MOLEC BIOL, D-82152 MARTINSRIED, GERMANY
[2] FAC MED NECKER ENFANTS MALAD, INSERM, U344, F-75730 PARIS, FRANCE
关键词
Jak2; prolactin; prolactin receptor; protein tyrosine phosphatase 1D; signal transduction;
D O I
10.1002/j.1460-2075.1996.tb00341.x
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
Stimulation of the prolactin receptor (PRLR), a member of the cytokine/growth hormone receptor family, results in activation of the associated Jak2 tyrosine kinase and downstream signaling pathways. We report that PTP1D, a cytoplasmic protein tyrosine phosphatase containing two Src homology 2 (SH2) domains, physically associates with the PRLR-Jak2 complex and is tyrosine-phosphorylated upon stimulation with prolactin. The formation of the trimeric PRLR-Jak2-PTP1D complex is critical for transmission of a lactogenic signal, while PTP1D phosphorylation is necessary, but not sufficient. The dominant negative inhibitory effect of a phosphatase-deficient mutant on expression of a beta-casein promoter-controlled reporter gene is evidence for an essential role of fully functional PTP1D in the regulation of milk protein gene transcription.
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页码:135 / 142
页数:8
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