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Trends Biochem Sci. 2009 Sep;34(9):443-52. doi: 10.1016/j.tibs.2009.06.002. Epub 2009 Sep 3.

Focus on the splicing of secretin GPCRs transmembrane-domain 7.

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GPCR Pathophysiology Group, Division of Endocrinology and Metabolism, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.


The family of G-protein coupled receptors (GPCRs) is one of the largest protein families in the mammalian genome with a fundamental role in cell biology. GPCR activity is finely tuned by various transcriptional, post-transcriptional and post-translational mechanisms. Alternative pre-mRNA splicing is now emerging as a crucial process regulating GPCR biological function. Intriguingly, this mechanism appears to extensively target the Secretin family of GPCRs, especially the exon that encodes a 14 amino acid sequence that forms the distal part of 7th transmembrane helix, and exhibits an unusually high level of sequence conservation among most Secretin GPCRs. Do the "TMD7-short" receptor variants have a role as novel regulators of GPCR signallng and, if so, what are the implications for hormonal actions and physiology?

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