PLACENTAL LACTOGEN-I VARIANT UTILIZES THE PROLACTIN RECEPTOR SIGNALING PATHWAY

Placenta lactogen-I variant (PL-Iv) is a member of a family of protein s expressed by the rat placenta with characteristics similar to prolac tin (PRL). In this report, we present the molecular cloning, chromosom al localization, and heterologous expression of PL-IV. Nucleotide sequ ence 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 car ries other members of the PRL gene family. PL-IV heterologously expres sed in Chinese Hamster ovary (CHO) cells exhibited similar immunoreact ive and electrophoretic characteristics with PL-Iv produced by the rat placenta. N-terminal sequencing verified the identity and purity of t he recombinant PL-Iv species and the site of cleavage of the signal pe ptide from the mature secreted PL-IV species. Recombinant PL-IV was sh own to bind to ovarian and liver PRL receptors, stimulate the prolifer ation of Nb2 lymphoma cells, and activate Jak2. Each of these actions is consistent with PL-IV utilizing the PRL receptor signal transductio n pathway.