This missense mutation is located in the third intracellular loop of SST5, a critical region for G protein coupling, and functional studies have demonstrated that mutant R240W receptor failed to mediate the inhibition of GH release and cell proliferation induced by SSTR5 agonist, although it retained the ability to inhibit intracellular cAMP levels, as the result of a loss of coupling with G oA protein but not with the other G proteins activated by wild type SSTR5, e.g., G i1, i2, i3 and G oB (11, 42)
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The research on tirzepatide reflects this