Prolactin recruits STAT1, STAT3 and STAT5 independent of conserved receptor tyrosines TYR402, TYR479, TYR515 and TYR580
Prolactin recruits STAT1, STAT3 and STAT5 independent of conserved receptor tyrosines TYR402, TYR479, TYR515 and TYR580
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DOI：
10.1016/0303-7207(95)03738-1
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发表时间：
1996-03-25
影响因子：
4.1
通讯作者：
Farrar, WL
中科院分区：
文献类型：
--
作者：
DaSilva, L;Rui, H;Farrar, WL
目前对催乳素 (PRL) 受体介导的信号转导子和转录激活子 (STAT) 募集的研究表明，除了先前报道的 STAT1 和 STAT5 之外，PRL 还激活 STAT3，并且 STAT1、STAT3 和 STAT5 是细胞中 PRL 作用的介质，无论是淋巴、骨髓还是乳腺上皮来源的细胞。此外，不介导PRL诱导的JAK2激活和细胞增殖的受体突变体M240和T280也不能介导STAT激活，支持JAK2作为PRL受体使用的初始效应蛋白的提议模型。另一方面，酪氨酸磷酸化分析和电泳迁移率变动分析表明，受体突变体G328缺乏PRL受体五个保守胞质酪氨酸残基中的四个，保留了激活JAK2和STAT1、STAT3和STAT5的能力。这些结果支持这样的观点：除受体（即 JAK2）之外的磷酸酪氨酰残基参与将 STAT 蛋白募集到激活的 PRL 受体复合物中。
The present study of prolactin (PRL) receptor-mediated recruitment of signal transducers and activators of transcription (STATs) demonstrates that PRL activates STAT3, in addition to STAT1 and STAT5 as previously reported, and that STAT1, STAT3 and STAT5 are mediators of PRL effects in cells whether of lymphoid, myeloid or mammary epithelial origin. Furthermore, receptor mutants M240 and T280 that do not mediate PRL-induced JAK2 activation and cell proliferation, are also unable to mediate STAT activation, supporting the proposed model of JAK2 as the initial effector protein used by PRL receptors. On the other hand, tyrosine phosphorylation analysis and electrophoretic mobility shift assays showed that receptor mutant G328, which lacks four of the five conserved cytoplasmic tyrosine residues of PRL receptors, retained the ability to activate JAK2 and STAT1, STAT3 and STAT5. These results support the notion that phosphotyrosyl residues other than those of the receptor, i.e., JAK2, are involved in recruiting STAT proteins to the activated PRL receptor complex.