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Bombesin Receptor

The family of G protein-coupled mammalian bombesin receptors comprises the gastrin-releasing peptide receptor (GRP-R or BB2-receptor), the neuromedin B receptor (NMB-R or BB1-receptor) and the orphan bombesin receptor subtype-3 (BRS-3 or BB3-receptor). These of G protein-coupled receptors mediate biological effects of bombesin related peptides (BLP). The amphibian regulatory peptide bombesin and its mammalian homologue GRP bind with high affinity to the GRP-R, whereas NMB selectively binds to the NMB preferring receptor NMB-R. No native ligand has been identified for the orphan BRS-3. Both regulatory BLPs, GRP and NMB, are processed from larger precursor molecules and are found widely distributed in the central nervous system (CNS) and in various peripheral tissues, such as neuronal elements of the gastrointestinal submucosal and myenteric plexus. Their biological effects include a broad range of important physiological and pathophysiological functions in health and disease. 
GRP and NMB both exert effects on cell growth and differentiation in various epithelial cell derived tumors. In addition, GRP stimulates secretion from the pancreas, release of gastrointestinal hormones, smooth muscle contraction and affects immune cells. Furthermore, GRP affects the CNS, including regulation of the circadian rhythm, anxiety and fear responses as well as thermoregulation; owing to its expression in the spinal cord, GRP has been recently also associated with the chronic itch sensation and penile reflexes. Tumors of the lung, prostate, head and neck, CNS, pancreas and colon have been shown to exhibit mitogenic response to GRP and NMB, whereby agonist signals generally activate the Raf-MEK-ERK mitogen-activated protein kinase cascade. In colorectal cancer cells, it was demonstrated that GRP activated focal adhesion kinase (FAK) and upregulated intracellular adhesion molecule (ICAM)-1 expression thereby promoting cell motility and attachment to the extracellular matrix.  In neuroblastoma cells, bombesin induced the expression of angiogenic markers, including platelet/endothelial cell adhesion molecule (PECAM)-1, vascular endothelial growth factor (VEGF) and elevated p-AKT levels, whereas GRP or GRP-R silencing significantly inhibited these changes.In prostate cancer cells, bombesin can mediate androgen receptor activity in a Src-dependent manner and possibly also involve nonreceptor tyrosine kinases focal adhesion kinase (FAK) and Etk/Bmx.

References

1.Weber HC,et al. Curr Opin Endocrinol Diabetes Obes. 2009 Feb;16(1):66-71.