The PRL responsiveness of target cells is negatively regulated by receptor internalization, ubiquitination and degradation, which limit the duration and intensity of receptor signaling (Djiane et al. 1981, 1982, Lu et al. 2002). The PRLR is phosphorylated on Ser-349 by an unidentified kinase (Li et al. 2006) enabling subsequent recruitment of the SCF beta-TrCP ubiquitin ligase complex (Li et al. 2004).