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

PTP1D is a positive regulator of the prolactin signal leading to beta-casein promoter activation
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DOI:
10.1002/j.1460-2075.1996.tb00341.x
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发表时间:
1996-01-02
期刊:
影响因子:
11.4
通讯作者:
Ullrich, A
Ullrich, A
中科院分区:
生物学1区
文献类型:
--
作者:
Ali, S;Chen, ZJ;Ullrich, A

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催乳素受体(PRLR)是细胞因子/生长激素受体家族的一员,刺激催乳素受体(PRLR)可激活相关的Jak2酪氨酸激酶和下游信号通路。我们报道,PTP1D是一种细胞质蛋白酪氨酸磷酸酶,含有两个Src同源2 (SH2)结构域,与PRLR-Jak2复合物物理结合,在催乳素刺激下酪氨酸磷酸化。三聚体PRLR-Jak2-PTP1D复合物的形成对于乳源信号的传递至关重要,而PTP1D磷酸化是必要的,但不是充分的。磷酸酶缺陷突变体对β -酪蛋白启动子控制的报告基因表达的显性负抑制作用证明了全功能PTP1D在调节乳蛋白基因转录中的重要作用。
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.