Clevenger Charles V, Gadd Samantha L, Zheng Jiamao
Department of Pathology and Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA.
Trends Endocrinol Metab. 2009 Jul;20(5):223-9. doi: 10.1016/j.tem.2009.03.001. Epub 2009 Jun 15.
Prolactin (PRL) is a pleiotrophic hormone that contributes to the growth of normal and malignant breast tissues. PRL signals through its receptor (PRLr), a transmembrane receptor that belongs to the cytokine receptor family. The mechanism of how the PRL:PRLr interaction triggers activation of signaling networks remains enigmatic. This review examines the effect of ligand binding on PRLr and the processes that initiate receptor-associated signaling. Evidence for PRLr predimerization in the absence of ligand and the actions of the prolyl isomerase cyclophilin A in ligand-induced activation of PRLr-associated Jak2 kinase are discussed. These studies reveal that ligand-induced conformational change of the PRLr complex is necessary for its function and open avenues for therapies to inhibit PRLr action in breast cancer.
催乳素（PRL）是一种具有多种功能的激素，对正常和恶性乳腺组织的生长均有作用。PRL通过其受体（PRLr）进行信号传导，PRLr是一种属于细胞因子受体家族的跨膜受体。PRL与PRLr相互作用如何触发信号网络激活的机制仍不清楚。本综述探讨了配体结合对PRLr的影响以及启动受体相关信号传导的过程。讨论了在无配体情况下PRLr预二聚化的证据以及脯氨酰异构酶亲环素A在配体诱导的PRLr相关Jak2激酶激活中的作用。这些研究表明，配体诱导的PRLr复合物构象变化对其功能至关重要，并为抑制乳腺癌中PRLr作用的治疗开辟了途径。
