Cytokine-inducible SH2-containing protein suppresses PRL signaling by binding the PRL receptor
Cytokine-inducible SH2-containing protein suppresses PRL signaling by binding the PRL receptor
复制标题
DOI：
10.1210/en.142.12.5286
复制
发表时间：
2001-12-01
期刊：
影响因子：
4.8
通讯作者：
Edery, M
中科院分区：
文献类型：
--
作者：
Dif, F;Saunier, E;Edery, M
在转染HEK 293细胞中，研究细胞因子信号抑制因子(SOCS)/细胞因子诱导的含sh2蛋白（CIS）对PRL激素信号的抑制作用。我们使用与生理相关的野生型β -酪蛋白启动子作为PRL作用的靶基因。我们证明CIS通过不同于SOCS-1对JAK2的作用的下游机制产生70%的PRL信号抑制。这种抑制涉及到与PRL受体（PRLR）的关联，导致信号换能器和转录激活因子5 （STAT5）激活的抑制。此外，我们发现SOCS-3与PRLR共免疫沉淀。这些数据表明，除了JAK2抑制外，SOCS-3还涉及另一种抑制PRL信号的途径。进一步的结果表明，SOCS-2可以在PRL信号传导中发挥更重要的增强作用，使SOCS-3诱导的转录抑制恢复50%，CIS诱导的转录抑制恢复100%。SOCS-2能够阻断SOCS-1的抑制作用。这些结果表明，SOCS-2似乎是其他SOCS的拮抗剂。SOCS-1结合JAK2并抑制其磷酸化；SOCS-3不结合JAK2，但结合可能介导其抑制JAK2的PRLR；最后，CIS结合PRLR，但抑制转录5的信号转换器和激活因子，而不是JAK2。
Inhibition of PRL hormone signaling by suppressor of cytokine signaling (SOCS)/cytokine-inducible SH2-containing protein (CIS) was investigated in transfected HEK 293 cells. We used the physiologically relevant wild-type beta -casein promoter as a target gene for PRL action. We demonstrate that CIS produces a 70% inhibition of PRL signaling by a mechanism distinct from, and downstream of, the effect of SOCS-1 on JAK2. This inhibition involves association with the PRL receptor (PRLR), resulting in the inhibition of signal transducer and activator of transcription 5 (STAT5) activation. Further, we show that SOCS-3 coimmunoprecipitates with the PRLR. These data suggest that SOCS-3 involves a second pathway for the inhibition of PRL signaling other than JAK2 inhibition. Additional results indicate that SOCS-2 can play a more important potentiator role on PRL signaling, resulting in a restoration of 50% of transcriptional inhibition induced by SOCS-3 and a restoration of 100% of transcriptional inhibition induced by CIS. SOCS-2 was able to block the inhibitory effect of SOCS-1. These results indicate that SOCS-2 seems to be an antagonist of the other SOCS. SOCS-1 binds JAK2 and inhibits its phosphorylation; SOCS-3 does not bind JAK2 but binds the PRLR that may mediate its inhibition of JAK2; and finally, CIS binds the PRLR but inhibits signal transducer and activator of transcription 5 rather than JAK2.