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American Zoologist 2000 40(2):269-286; doi:10.1093/icb/40.2.269
© 2000 by The Society for Integrative and Comparative Biology
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Structure-Function Relationships of the Signaling System for the Somatostatin Peptide Hormone Family1

Mark A. Sheridan2,1, Jeffrey D. Kittilson1 and Barton J. Slagter1
1 Department of Zoology and Regulatory Biosciences Center, North Dakota State University, Fargo, North Dakota 58105

Somatostatins are a diverse family of peptide hormones that regulate a vast array of biological processes in vertebrates, including the modulation of growth, development, and metabolism. The multi-functional nature of the somatostatin family arises from the an elaborate, multi-faceted signaling system consisting of somatostatin signaling molecules, G-protein-coupled receptors, and cellular effector pathways. A striking aspect of this signaling system is the substantial diversity at every level. The signal molecules themselves display considerable structural heterogeneity. This molecular heterogeneity results from tissue-specific differential processing of a single large precursor protein (preprosomatostatin) as well as from the existence of multiple somatostatin genes, each giving rise to different precursors. In addition, numerous SS receptor subtypes have been characterized (five in mammals), some of which exhibit preferential binding to one ligand form over another. Propagation of the signal results from linkage of the receptors via numerous types of G-proteins to several different cellular effector pathways, including adenylyl cyclase, various protein kinases, numerous ion channels, and phospholipase C/inositol-3-phosphate. Ultimately, a particular response in a given target cell may be determined by structural interactions between and among the various elements of the signaling system.


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