Cloning and Characterization of a cDNA Encoding a Highly Conserved Ca²⁺-Binding Protein, Identified by an Anti-Prolactin Receptor Antibody

Abstract

Prolactin receptors are found in many tissues (Posner et al. 1974), which suggests that prolactin may have multiple functions. Certainly prolactin has been shown to exert a wide variety of activities in different species (Nicoll and Bern 1972). The molecular mechanisms which mediate the physiological actions of prolactin are, however, unknown. Although the specific interaction of the hormone with its cell surface receptor on target cells is the first step, the subsequent mechanism(s) of signal transduction is unknown. The recent cloning of the prolactin (Boutin et al. 1988) and growth hormone (Leung et al. 1987) receptors has revealed that they is a new class of membrane receptors without sequence similarities to other known membrane receptors. Moreover, there appear to be at least two different forms of the prolactin receptor, a short and a long form. The major mRNA species for the prolactin receptor in the rat liver is 2.2 kb, whereas the major species in the rat mammary gland is 4 kb (Boutin et al. 1988). Prolactin receptor cDNAs have also been isolated from rabbit mammary gland (Edery et al. 1989) and T-47D human breast cancer cells (Boutin et al. 1989) and these cDNAs predict mRNAs which encode 592 and 598 amino acid residue mature proteins, respectively. These are in contrast to the 291 amino acid residue mature protein predicted from the rat liver cDNA. The difference between the two forms of the prolactin receptor resides primarily in the cytoplasmic domain, 57 residues for the rat liver prolactin receptor versus 358 for the rabbit mammary gland receptor (Edery et al. 1989; Boutin et al. 1989). Due to this variability in the size of the mature prolactin receptor protein, it is possible that multiple mechanisms of signal transduction may occur for prolactin receptor, in a species- and tissue-specific manner.