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细胞功能测定>Selective Antagonism of Receptor Signaling Using Antisense RNA to Deplete G-Protein Subunits
Selective Antagonism of Receptor Signaling Using Antisense RNA to Deplete G-Protein Subunits
关键词: selective antagonism receptor来源: 互联网
The molecular identification and characterization of the components of receptor-signaling pathways has revealed a striking redundancy and diversity of signaling elements. For example, G protein-coupled receptors bind to a diversity of ligands, ranging from classical low-molecular-weight monoammes like serotonin (5HT) or dopamine, to large glycoproteins such as gonadotropins (1 ). Within a given receptor family, multiple subtypes of receptors have been identified: for example, the serotonin-receptor family comprises over 15 distinct receptors (2 ). An analogous multiplicity of subtypes extsts within the families of G proteins (3 ,4 ) and effecters, such as phospholipases, adenylyl cyclases, protein kinases, and ion channels (5 –9 ). Indeed, low-stringency cDNA-screening techmques have led to the identification of homologs of unknown function, such as orphan receptors (10 ). Biochemical characterization of purified proteins in vitro, or by overexpression of then cDNAs in transfected cell lines has been instrumental in defining the properties of these signal-transduction elements. However, these approaches may distort the interactions that occur in situ because of abnormally high expression of the various signaling components and nonphysiological optimization of assay conditions. Pharmacological approaches have been very useful in defining the physiological roles of cloned receptors, but are limited by the availability of specific receptor agonists and antagonists.
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