Role Of Phosphorylation In Tp Receptor Desensitizatton

Sites of agonist-induced TP receptor phosphorylation on serine-threonine residues in the third extracellular loop and the carboxyl-terminal tail of TP receptor fusion proteins have been identified by the use of competitive synthetic peptides, and roles for PKC and protein kinase A (PKA) have been defined (66). Other kinases may contribute to phosphorylation of TP receptors following activation (60). Antagonist ([3H]-SQ29548) binding to TP receptors expressed in transfected HEL cells was inhibited following incubation with PMA, presumably as a result of TP receptor phosphorylation (66). More recent studies of agonist-dependent TP receptor isoform phosphorylation demonstrated a 2-3 fold increase in basal phosphorylation of transfected TP receptors in response to PMA, and a reduction in basal phosphorylation of both TP-a and TP-P receptors in response to PKC inhibition (60). The role of PKC and PKA in agonist-induced TP phosphorylation is uncertain (60,66). Therefore, other kinases, such as GPCR-dependent kinases, may play a role in vivo (60); however, a TP receptor-dependent kinase has not been described.

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