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This version published online on August 1, 2002
Molecular Endocrinology, doi:10.1210/me.2001-0033
Molecular Endocrinology Vol. 0, No. 2002 200100331-
doi:10.1210/me.2001-0033
Copyright © 2002 by the Endocrine Society.
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Submitted on April 30, 2001
Accepted on July 16, 2002

Characterization of a Novel and Functional Human PRL Receptor Isoform ({Delta}S1PRLr) Containing Only One Extracellular Fibronectin-like Domain

J. Bradford Kline1, Michael A. Rycyzyn1, and Charles V. Clevenger1*

1 Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA 19104

* To whom correspondence should be addressed. E-mail: clevengc{at}mail.med.upenn.edu.

Prolactin-dependent signaling occurs as the result of ligand-induced homodimerization of the PRL receptor (PRLr). To date, both intermediate and long human PRLr isoforms have been characterized. To investigate the expression of other possible human PRLr isoforms, reverse transcription polymerase chain reaction (RT-PCR) was performed on mRNA isolated from the breast carcinoma cell line T47D. A 1.5-kilobase pair PCR fragment was isolated, subcloned, and sequenced. The PCR product exhibited a nucleotide sequence 100% homologous to the human long isoform except basepairs 71 to 373 were deleted, which code for the S1 motif of the extracellular domain (ECD). Therefore, this isoform was designated the {Delta}S1 PRLr. Northern analysis revealed variable {Delta}S1 PRLr mRNA expression in a variety of tissues. Transfection of CHO cells with {Delta}S1 cDNA showed the isoform is expressed at the protein level on the cell surface with a molecular weight of approximately 70 kDa. Kinetic studies indicated the {Delta}S1 isoform bound ligand at a lower affinity than wild-type receptor. The {Delta}S1 PRLr was also shown to activate the proximal signaling molecule Jak2 upon addition of ligand to transfected cells, and unlike the long PRLr, high concentrations of ligand did not function as a self-antagonist to signaling during intervals of PRL serum elevation, i.e. stress and pregnancy. Given its apparent widespread expression, this PRLr isoform may contribute to PRL action. Furthermore, the functionality of this receptor raises interesting questions regarding the minimal ECD necessary for ligand-induced receptor signaling.
Key words: PRL • PRL receptor • receptor isoform • surface plasmon resonance • GH • placental lactogen




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