+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Alternative splicing to exon 11 of human prolactin receptor gene results in multiple isoforms including a secreted prolactin-binding protein



Alternative splicing to exon 11 of human prolactin receptor gene results in multiple isoforms including a secreted prolactin-binding protein



Journal of Molecular Endocrinology 30(1): 31-47



Endocrine and autocrine prolactin (PRL) exerts effects on normal breast and breast cancer cells, and high serum PRL is a poor prognostic factor for colorectal cancer. Here we tested the hypothesis that short isoforms of the PRL receptor (PRLR) in human tissue regulate the actions of PRL in cancer. Using 3' RACE we isolated five splice variants of the human PRLR (hPRLR), three of which encode the complete extracellular binding domain. Two of these isoforms, short form 1a (SF1a) and short form 1b (SF1b), possess unique intracellular domains encoded by splicing to exon 11 from exons 10 and 9 respectively. A third novel isoform (DELTA7/11) reflects alternative splicing from exon 7 to exon 11 and encodes a secreted soluble PRL-binding protein. Additional splice variants of SF1b and DELTA7/11 that lacked exon 4 (DELTA4-SF1b and DELTA4-DELTA7/11) were also identified. Functional analyses indicated that hPRLR-SF1b is a strong dominant-negative to the differentiative function of the PRLR long form while hPRLR-SF1a is a weaker dominant-negative. Differential abundance of SF1a, SF1b and DELTA7/11 expression was detected in normal breast, colon, placenta, kidney, liver, ovary and pancreas, and breast and colon tumors. Taken together, these data indicate the presence of multiple isoforms of the hPRLR that may function to modulate the endocrine and autocrine effects of PRL in normal human tissue and cancer.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 010149884

Download citation: RISBibTeXText

PMID: 12580759

DOI: 10.1677/jme.0.0300031


Related references

Mouse prolactin receptor gene: genomic organization reveals alternative promoter usage and generation of isoforms via alternative 3'-exon splicing. Dna and Cell Biology 17(9): 761-770, 1998

Alternative splicing of the prolactin receptor gene generates a 1.7 kb RNA transcript that is linked to prolactin function in the red deer testis. Journal of Molecular Endocrinology 21(1): 51-59, 1998

Isolation and characterization of two novel forms of the human prolactin receptor generated by alternative splicing of a newly identified exon 11. Journal of Biological Chemistry 276(44): 41086-41094, 2001

Differential effects of sex steroid hormones on the expression of multiple first exons including a novel first exon of prolactin receptor gene in the rat liver. Journal of Molecular Endocrinology 34(3): 667-673, 2005

Polypyrimidine tract-binding protein represses splicing of a fibroblast growth factor receptor-2 gene alternative exon through exon sequences. Journal of Biological Chemistry 276(47): 43677-43687, 2001

Multiple new isoforms of the human prolactin receptor gene. Advances in Experimental Medicine and Biology 554: 495-499, 2004

Multiple isoforms of HRNBP2, a splicing enhancer for erythroid protein 41R exon 16, are encoded by a complex gene via alternative pre-mRNA processing events. Blood 102(11): 7a, 2003

The alternate stimulation or suppression of prolactin gene transcription by l triiodothyronine is mediated by multiple receptor binding motifs within the proximal prolactin gene. Journal of Cellular Biochemistry Suppl. 15(Part E): 7, 1991

Secreted mouse prolactin and stored ovine prolactin 2. role of amides in receptor binding and immunoreactivity. Endocrinology 116(1): 353-358, 1985

Alternative splicing of Wilms tumor suppressor 1 (Wt1) exon 4 results in protein isoforms with different functions. Developmental Biology 393(1): 24-32, 2014

Alternative splicing of a 48-nucleotide exon generates two isoforms of the human calcitonin receptor. Endocrinology 136(5): 2047-2051, 1995

The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. Journal of Biological Chemistry 266(18): 11947-11954, 1991

Alternative-splicing in the exon-10 region of GABA(A) receptor beta(2) subunit gene: relationships between novel isoforms and psychotic disorders. Plos one 4(9): E6977, 2009

Molecular characterization of prolactin receptor (cPRLR) gene in chickens: gene structure, tissue expression, promoter analysis, and its interaction with chicken prolactin (cPRL) and prolactin-like protein (cPRL-L). Molecular and Cellular Endocrinology 370(1-2): 149-162, 2013

The human AKNA gene expresses multiple transcripts and protein isoforms as a result of alternative promoter usage, splicing, and polyadenylation. Dna and Cell Biology 24(5): 325-338, 2005