DaSilva L, Rui H, Erwin R A, Howard O M, Kirken R A, Malabarba M G, Hackett R H, Larner A C, Farrar W L
SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA.
Mol Cell Endocrinol. 1996 Mar 25;117(2):131-40. doi: 10.1016/0303-7207(95)03738-1.
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.
目前关于催乳素（PRL）受体介导的信号转导子和转录激活子（STATs）募集的研究表明，PRL除了如先前报道的激活STAT1和STAT5外，还激活STAT3，并且STAT1、STAT3和STAT5是PRL在淋巴细胞、髓细胞或乳腺上皮来源的细胞中发挥作用的介质。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，也无法介导STAT激活，这支持了将JAK2作为PRL受体使用的初始效应蛋白的模型。另一方面，酪氨酸磷酸化分析和电泳迁移率变动分析表明，缺乏PRL受体五个保守细胞质酪氨酸残基中的四个的受体突变体G328，保留了激活JAK2以及STAT1、STAT3和STAT5的能力。这些结果支持这样一种观点，即除了受体的酪氨酸残基（即JAK2）外，其他磷酸化酪氨酸残基也参与将STAT蛋白募集到活化的PRL受体复合物中。
