tokens: We previously showed that this proteolysis 1 ) can be acutely promoted by the phorbol ester phorbol 12 - myristate 13 - acetate ( PMA ) , 2 ) requires a metalloprotease activity , 3 ) generates both shed GHBP and a membrane - associated GHR transmembrane / cytoplasmic domain remnant , and 4 ) results in down - regulation of GHR abundance and GH signaling .