The response of target cells to the polypeptide hormone, prolactin, is initiated by the inaction of the hormone with a cell surface receptor that belongs to the class of receptors with a single membrane-spanning domain, designated as the cytokine/GH/PRL receptor family. The mechanism of signal transduction for this family of receptors is not yet determined. Cloning and functional analysis of different forms of the prolactin receptor (PRL-R) were carried out to elucidate the mechanism of signal transduction. The protein sequence deduced from cDNAs isolated from a rat ovarian cDNA library revealed the existence of a long form of the PRL-R in the rat. The mature form has a predicted size of 591 amino acids and shows strong overall sequence similarity with previously cloned long forms of the PRL-R from other species. Another form of the PRL-R was characterized in Nb$ sb2$ cells, a rat lymphoma cell line, dependent on PRL for mitogenesis. This receptor is a deleted form of the long form of the PRL-R missing 198 amino acids in the cytoplasmic domain. The ability of the different forms of the PRL-R to transmit a lactogenic signal was tested in functional systems. The systems consisted of the transient co-transfection of chinese hamster ovary (CHO) cells with a fusion gene containing a milk protein gene promoter linked to the chloramphenicol acetyl transferase (CAT) gene coding region and an expression vector containing various forms of PRL-R cDNAs under the control of the SV-40 early promoter. CAT activity was measured three days after transfection. Results indicate that the long form of the PRL-R is capable of transmitting PRL's signal and activating the milk protein gene promoter. However, when the short form of the receptor was transfected, there was no induction of CAT activity. Interestingly, the Nb$ sb2$ form of the PRL-R was fully capable of transmitting PRL's signal, when examined in the above functional system. This implies that the 198 amino acids segment of t
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.41286 |
| Date | January 1993 |
| Creators | Ali, Suhad Kamil M. |
| Contributors | Kelly, Paul A. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001351733, proquestno: NN91822, Theses scanned by UMI/ProQuest. |
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