IMMUNE FUNCTION OF PROLACTIN (PRL) AND SIGNAL-TRANSDUCTION BY PRL GH/CYTOKINE RECEPTORS - SPECIFICITY, REDUNDANCY AND LESSONS FROM CHIMERAS/

Although prolactin (PRL) was originally regarded exclusively as a lact ogenic hormone, there are a number of observations that suggest a role for this protein in the regulation of immune responses. The first ste p in understanding this unexpected function came from the cloning of t he prolactin receptor, which was later shown to be a member of the cyt okine receptor superfamily. The PRL receptor shares structural analogi es with receptors for proteins acting on immune cells, the prototype o f which is IL-2. Studies of cytokine receptor signalling revealed that all messages are transmitted in the cell through a limited set of tra nsducers, among which the JAK kinases and the Stat transcription facto rs represent a major cascade. Deciphering the rules allowing a given c ytokine receptor, and not another, to activate a particular set of JAK and Stat proteins is a key step in understanding functional specifici ties within this receptor superfamily. Mutational analyses have provid ed interesting information about which features are required for which property. Much less data are available from studies using chimaeric r eceptors, although this strategy is probably more powerful for compari ng different receptors and addressing the question of their specificit y (or redundancy). As frequently as possible, we shall illustrate our discussions through experimental investigations using the chimaeric ap proach.