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参与小鼠乳腺组织中催乳素信号转导的Stat5及另一个同源物(Stat5b)的克隆与表达

Cloning and expression of Stat5 and an additional homologue (Stat5b) involved in prolactin signal transduction in mouse mammary tissue.

作者信息

Liu X, Robinson G W, Gouilleux F, Groner B, Hennighausen L

机构信息

Laboratory of Biochemistry and Metabolism, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8831-5. doi: 10.1073/pnas.92.19.8831.

DOI:10.1073/pnas.92.19.8831
PMID:7568026
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC41061/
Abstract

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.

摘要

催乳素(PRL)通过包含Janus激酶Jak2和乳腺因子(MGF;也称为Stat5)的信号级联反应,诱导乳蛋白基因的转录激活,如乳清酸性蛋白(WAP)、β-酪蛋白和β-乳球蛋白基因,Stat5属于信号转导和转录激活蛋白(STAT)家族。我们从小鼠乳腺组织中分离并测序了Stat5 mRNA和一个以前未报道的成员,我们将其命名为Stat5b(Stat5现重新命名为Stat5a)。在蛋白质水平上,Stat5a和Stat5b的序列相似性为96%。两种mRNA的5'和3'非翻译区不保守。Stat5a由793个氨基酸组成,由一个4.2 kb的mRNA编码。Stat5b mRNA大小为5.6 kb,编码一个786个氨基酸的蛋白质。Stat5a和Stat5b在体外都能识别GAS位点(γ-干扰素激活序列;TTCNNNGAA),并在转染了PRL受体的COS细胞中介导PRL诱导的转录。Stat5b在无PRL的情况下也能诱导基础转录。在未成熟处女鼠和泌乳小鼠的大多数组织中,Stat5a和Stat5b mRNA的水平相似,但在肌肉和乳腺组织中发现了Stat5 mRNA的差异积累。这两种RNA存在于未成熟处女鼠的乳腺组织中,其水平在怀孕第16天之前升高,随后在泌乳期间下降。怀孕期间Stat5表达的增加与WAP基因的激活同时发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f47/41061/a18658bae194/pnas01497-0311-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f47/41061/3a3770cc84ec/pnas01497-0310-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f47/41061/e010ef39d06f/pnas01497-0311-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f47/41061/a18658bae194/pnas01497-0311-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f47/41061/3a3770cc84ec/pnas01497-0310-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f47/41061/e010ef39d06f/pnas01497-0311-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f47/41061/a18658bae194/pnas01497-0311-b.jpg

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Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins.Jak-STAT信号通路以及对干扰素和其他细胞外信号蛋白的转录激活。
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