Figure 1.

Parallels between prolactin and steroid-induced signal transduction. Classic theory has the prolactin (PRL)/prolactin receptor effecting gene expression 'at-a-distance' through actions of receptor-associated signaling networks, such as the Jak2/Stat5 and Raf/mitogen-activated protein kinase (MAPK) pathways. A growing body of evidence indicates, however, that following receptor-mediated endocytosis a complex between PRL and cyclophilin B (CypB) undergoes nuclear retrotranslocation, possibly through the Sec61 pore. Within the nucleus, the PRL/CypB complex binds to repressed Stat5 complexes, inducing the release of peptide inhibitor of activated Stat3 (PIAS3) enabling Stat5 to engage DNA. In addition, the PRL/CypB complex interacts with other elements of the transcriptional apparatus (Tfx). Like PRL/CypB, steroid/steroid receptors (GR) are also able to translocate into the nucleus, where they act as transcription factors. In contrast to these genomic actions of steroid receptors, the nongenomic actions of steroid/steroid receptor complexes occur at the cell surface, are rapid, and utilize some of the same signaling networks utilized by the polypeptide ligand/receptor complexes (i.e. MAPK). ER, endoplasmic reticulum.