New mechanisms for PRLr action in breast cancer.
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.
Clevenger
Charles V
CV
Department of Pathology and Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA. clevenger@northwestern.edu
Gadd
Samantha L
SL
Zheng
Jiamao
J
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D021984:Cyclophilin A / Q000494:pharmacology; D005260:Female; D006801:Humans; D008954:Models, Biological; D011388:Prolactin / Q000378:metabolism / Q000502:physiology*; D055503:Protein Multimerization; D011981:Receptors, Prolactin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D011981:Receptors, Prolactin; D011388:Prolactin; D021984:Cyclophilin A