Research for the molecular mechanism regulating multu-functresponses mediated via G protein-coupled receptors

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Since the ligands to G protein coupled receptors (GPCRs) are utilized for the, treatment of many diseases, it is important to investigate the signal transduction in GPCRs for developing the new effective drugs. Recently, it has been clarified that stimulation of one GPCR results in the multiple responses, although the molecular mechanism has not been clarified. In the present study, we tried to clarify the mechanism in GPCR-mediated multiple signal transduction.To examine the protein directly bound to thromboxane A_2 receptor (TP), yeast two hybrid system was employed. It was found that carboxyl terminal of TP-β, but not TP-α, proteasome activator PA28γ and proteasome subunit α7. Furthermore, an inhibitor of proteasome accelerated, the expression of TP-β, but not TP-α. On the other hand, it has been examined whether TP communicates with G_<12> family G protein using the adenovirus coding the Gα_2 or Gα_<13>. We found that TP clearly communicate G_<12> and G_<13> in addition of Gq. Moreover, we found that C terminal of PTH receptor communicates with Tctex-1 and 4.1G, which show a role of internalization PTH receptor or expression of the receptor in plasma membranes, respectively. Thus, we clarify, the several important regulatory mechanism of GPCR-mediated signal transduction in the present study.