Phylogenetic analysis of the sequences of gastrin-releasing peptide and its receptors: biological implications.

Regul Pept 2007 Oct 27;143(1-3):1-14. Epub 2007 Feb 27.

University of Melbourne, Department of Surgery, Austin Health, Studley Rd., Heidelberg, Victoria 3084, Australia.

The many biological activities of the hormone gastrin-releasing peptide (GRP), including stimulation of acid secretion and of tumour growth, are mediated by the gastrin-releasing peptide receptor (GRP-R). Here sequence comparisons are utilised to investigate the likely bioactive regions of the 125 amino acid GRP precursor and of GRP-R. Comparison of the sequences of the GRP precursor from 21 species revealed homology not only in the GRP region between amino acids 1 and 30, but also in C-terminal regions from amino acids 43 to 97. This observation is consistent with recent reports that peptides derived from the C-terminal region are biologically active. Comparison of the GRP-R sequence with the related receptors NMB-R and BRS-3 revealed that the family could be distinguished from other G-protein coupled receptors by the presence of the motif GVSVFTLTALS at the cytoplasmic end of transmembrane helix 3. Comparison of the sequences of the GRP-R from 21 species revealed that the most highly conserved regions occurred in transmembrane helices 2, 3, 5, 6 and 7, and in the third intracellular loop. These results will be important in guiding future structure-function studies of the GRP precursor and of GRP receptors.

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http://dx.doi.org/10.1016/j.regpep.2007.02.007DOI Listing
October 2007

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