CLONING AND EXPRESSION OF STAT5 AND AN ADDITIONAL HOMOLOG (STAT5B) INVOLVED IN PROLACTIN SIGNAL-TRANSDUCTION IN MOUSE MAMMARY TISSUE
CLONING AND EXPRESSION OF STAT5 AND AN ADDITIONAL HOMOLOG (STAT5B) INVOLVED IN PROLACTIN SIGNAL-TRANSDUCTION IN MOUSE MAMMARY TISSUE
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DOI：
10.1073/pnas.92.19.8831
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发表时间：
1995-09-12
影响因子：
11.1
通讯作者：
HENNIGHAUSEN, L
中科院分区：
文献类型：
--
作者：
LIU, XW;ROBINSON, GW;HENNIGHAUSEN, L
催乳素(PRL)诱导乳清酸性蛋白(WAP)、β-酪蛋白和β-乳球蛋白基因等乳清蛋白基因的转录激活，途径包括Janus激酶JAK2和乳腺因子(MGF；也被称为Stat5)，属于信号转导和转录激活因子(STAT)蛋白家族，我们从小鼠乳腺组织中分离并测序了Stat5mRNA和一个以前未报道的成员，命名为Stat5b(Stat5a更名为Stat5a)，在蛋白质水平上，Stat5a和Stat5b具有96%的序列相似性，两个mRNA5‘和3’非翻译区不保守，Stat5a由793个氨基酸组成，编码一个4.2kb的mRNA，其大小为5.6kb，编码一个786个氨基酸的蛋白质。Stat5a和Stat5b都识别气体位置(伽马干扰素激活序列；Stat5b在没有PRL的情况下也能诱导COS细胞的基础转录，在处女鼠和哺乳期小鼠的大多数组织中都发现了类似水平的Stat5a和Stat5b的mRNAs，但在肌肉和乳房组织中发现了Stat5mRNAs的差异积累，这两种RNA在未成熟的处女鼠的乳房组织中存在，并在妊娠第16天开始升高，随后在哺乳期下降，妊娠期间Stat5a和Stat5b基因的表达增加与WAP基因的激活一致。
Prolactin (PRL) induces transcriptional activation of milk protein genes, such as the whey acidic protein (WAP), beta-casein, and beta-lactoglobulin genes, through a signaling cascade encompassing the Janus kinase Jak2 and the mammary gland factor (MGF; also called Stat5), which belongs to the family of proteins of signal transducers and activators of transcription (STAT), We isolated and sequenced from mouse mammary tissue Stat5 mRNA and a previously unreported member, which we named Stat5b (Stat5 is renamed to Stat5a), On the protein level Stat5a and Stat5b show a 96% sequence similarity, The 5' and 3' untranslated regions of the two mRNAs are not conserved, Stat5a comprises 793 amino acids and is encoded by a mRNA of 4.2 kb, The Stat5b mRNA has a size of 5.6 kb and encodes a protein of 786 amino acids, Both Stat5a and Stat5b recognized the GAS site (gamma-interferon-activating sequence; TTCNNNGAA) in vitro and mediated PRL-induced transcription in COS cells transfected with a PRL receptor, Stat5b also induced basal transcription in the absence of PRL, Similar levels of Stat5a and Stat5b mRNAs were found in most tissues of virgin and lactating mice, but a differential accumulation of the Stat5 mRNAs was found in muscle and mammary tissue, The two RNAs are present in mammary tissue of immature virgin mice, and their levels increase up to day 16 of pregnancy, followed by a decline during lactation, The increase of Stat5 expression during pregnancy coincides with the activation of the WAP gene.