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Concept
Thromboxane receptor
Résumé
The thromboxane receptor (TP) also known as the prostanoid TP receptor is a protein that in humans is encoded by the TBXA2R gene, The thromboxane receptor is one among the five classes of prostanoid receptors and was the first eicosanoid receptor cloned. The TP receptor derives its name from its preferred endogenous ligand thromboxane A2.
The gene responsible for directing the synthesis of the thromboxane receptor, TBXA2R, is located on chromosome 19 at position p13.3, spans 15 kilobases, and contains 5 exons. TBXA2R codes for a member of the G protein-coupled super family of seven-transmembrane receptors.
Molecular biology findings have provided definitive evidence for two human TP receptor subtypes. The originally cloned TP from placenta (343 amino acids in length) is known as the α isoform and the splice variant cloned from endothelium (with 407 amino acids), termed the β isoform. The first 328 amino acids are the same for both isoforms, but the β isoform exhibits an extended C-terminal cytoplasmic domain. Both isoforms stimulate cells in part by activating the Gq family of G proteins. In at least certain cell types, however, TPα also stimulates cells by activating the Gs family of G proteins while TPβ also stimulates cells by activating the Gi class of G proteins. This leads to the stimulation or inhibition, respectively, of adenylate cyclase activity and thereby very different cellular responses. Differences in their C-terminal tail sequence also allow for significant differences in the two receptors internalization and thereby desensitization (i.e. loss of G protein- and therefore cell-stimulating ability) after activation by an agonist; TPβ but not TPα undergoes agonist-induced internalization.
The expression of α and β isoforms is not equal within or across different cell types. For example, platelets express high concentrations of the α isoform (and possess residual RNA for the β isoform), while expression of the β isoform has not been documented in these cells. The β isoform is expressed in human endothelium.
Source officielle
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