Immune function of prolactin (PRL) and signal transduction by PRL/GH/cytokine receptors: specificity, redundancy and lessons from chimaeras.

Although prolactin (PRL) was originally regarded exclusively as a lactogenic hormone, there are a number of observations that suggest a role for this protein in the regulation of immune responses. The first step in understanding this unexpected function came from the cloning of the prolactin receptor, which was later shown to be a member of the cytokine receptor superfamily. The PRL receptor shares structural analogies with receptors for proteins acting on immune cells, the prototype of which is IL-2. Studies of cytokine receptor signalling revealed that all messages are transmitted in the cell through a limited set of transducers, among which the JAK kinases and the Stat transcription factors represent a major cascade. Deciphering the rules allowing a given cytokine receptor, and not another, to activate a particular set of JAK and Stat proteins is a key step in understanding functional specificities within this receptor superfamily. Mutational analyses have provided interesting information about which features are required for which property. Much less data are available from studies using chimaeric receptors, although this strategy is probably more powerful for comparing different receptors and addressing the question of their specificity (or redundancy). As frequently as possible, we shall illustrate our discussions through experimental investigations using the chimaeric approach.