A pathway map of prolactin signaling

Abstract

Prolactin (PRL) is a pleiotropic polypeptide hormone secreted primarily by the lactotrophic cells of anterior pituitary gland in vertebrates (Freeman et al. 2000). This hormone family includes placental lactogen (PL) and growth hormone (GH) (Corbacho et al. 2002). Prolactin plays a major role in lactation and reproduction and has been shown to have a multitude of effects relating to growth, development, metabolism, immunoregulation and protection (Ben-Jonathan et al. 2006). The prolactin signaling pathway is initiated by the binding of prolactin with the prolactin receptor (PRLR), a member of class I cytokine receptor superfamily (Binart et al. 2000), which is expressed in a variety of tissues. The PRLR comprises of an extracellular ligand binding domain, a transmembrane domain and an intracellular domain. The PRLR lacks intrinsic kinase activity and transduces signal through kinases that interact with its cytoplasmic tail. Three constitutively active variants of the receptor have been reported in humans (Goffin et al. 2010). Though the signaling reactions downstream of the longest isoform of prolactin receptor have been well established, little is known about prolactin signaling initiated by six other isoforms (Bouilly et al. 2011). Studies also indicate that binding affinity of the human prolactin receptor to nonhuman prolactin is lower than human prolactin (Utama et al. 2009). The prolactin receptor also binds to hPL and hGH leading to the activation of downstream pathways. However, we have not considered these reactions in the current study. This study reports only those reactions, which occur upon stimulation of prolactin receptor with prolactin, based on the criteria described previously (Nanjappa et al. 2011). Availability of signaling pathway information is useful to the biomedical research community, especially for systems biology approaches. Considering this, we have developed ‘NetPath’ as a resource of ligand-receptor specific signal transduction pathways (Kandasamy et al. 2010). As a part of this, we have carried out manual annotation of available information from the published literature for ligand-receptor signaling pathways (Raju et al. 2011a; Nanjappa et al. 2011; Telikicherla et al. 2011; Goel et al. 2012). Similarly, in this study, we enriched publicly available information pertaining to prolactin-prolactin receptor dependent signaling pathways and also generated a graphic map depicting the prolactin signaling pathway.