Placental lactogen-I variant utilizes the prolactin receptor signaling pathway

Placenta lactogen-I variant (PL-Iv) is a member of a family of proteins expressed by the rat placenta with characteristics similar to prolactin (PRL). In this report, we present the molecular cloning, chromosomal localization, and heterologous expression of PL-Iv. Nucleotide sequence analysis of the PL-Iv cDNA clone predicted a precursor protein of 223 amino acids, including a 28-amino acid signal sequence. The PL-Iv gene was localized to chromosome 17 of the rat genome, which also carries other members of the PRL gene family. PL-Iv heterologously expressed in Chinese Hamster ovary (CHO) cells exhibited similar immunoreactive and electrophoretic characteristics with PL-Iv produced by the rat placenta. N-terminal sequencing verified the identity and purity of the recombinant PL-Iv species and the site of cleavage of the signal peptide from the mature secreted PL-Iv species. Recombinant PL-Iv was shown to bind to ovarian and liver PRL receptors, stimulate the proliferation of Nb2 lymphoma cells, and activate Jak2. Each of these actions is consistent with PL-Iv utilizing the PRL receptor signal transduction pathway.