Abstract
Human prolactin receptor (PRLR) transcripts and their protein products exhibit heterogenic structures and functions. This multiplicity constitutes a gene regulatory system. Short PRLR might modulate longer PRLR structures and signaling. Here we overviewed 10 forms (including two putative forms) of PRLR structures, signaling and functions and analyzed the possible regulatory system regarding multiple PRLRs. Particularly, we discovered that a mimic of phosphorylated prolactin induced p21 waf1 expression via a short form of PRLR S1b in prostate cancer cells. In addition, an intron retention was discovered in PRLR mRNA transcript via sequence analysis, showing that an intron encodes PRLR once needed. PRLR splicing and intron retention might be a critical modulating system to regulate PRLR structures and functions. Furthermore, PRLR genomic size was extended to 182 kb, versus the former report, 70 kb. Interestingly, dozens of PRLR-linked genes on chromosome 5 might interplay one another. This review fully uncovered the associations in PRLR multiplicity and functions, suggesting that shorter PRLR might modulate long PRLR function via multiple PRLR system in both mRNA and protein levels.
Highlights
Prolactin is a pituitary-secreted hormone, which functions via binding prolactin receptor (PRLR) and further activates a series of signaling pathways leading to necessary physiological actions in paracrine, autocrine and endocrine ways in vitro and in vivo (Ben-Jonathan et al, 2008; Goffin et al, 2005; Teilum et al, 2005)
It is believed that more and more human PRLR forms will be discovered including those, which might result from totally different genes
It has been noted that in PRL triggered response, the influence of growth hormone should not be ignored since growth hormone binds PRLR
Summary
Human prolactin receptor (PRLR) transcripts and their protein products exhibit heterogenic structures and functions. This multiplicity constitutes a gene regulatory system. Short PRLR might modulate longer PRLR structures and signaling. We overviewed 10 forms (including two putative forms) of PRLR structures, signaling and functions and analyzed the possible regulatory system regarding multiple PRLRs. we discovered that a mimic of phosphorylated prolactin induced p21 waf expression via a short form of PRLR S1b in prostate cancer cells. An intron retention was discovered in PRLR mRNA transcript via sequence analysis, showing that an intron encodes PRLR once needed. PRLR splicing and intron retention might be a critical modulating system to regulate PRLR structures and functions.
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