Interaction site of GTP binding Gh (transglutaminase II) with phospholipase C

Abstract

The GTP binding G alpha h (transglutaminase II) mediates the alpha 1B-adrenoreceptor signal to a 69-kDa phospholipase C (PLC). Thus, G alpha h possesses both GTPase and transglutaminase activities with a signal transfer role. The recognition sites of this unique GTP binding protein for either the receptor or the effector are completely unknown. A site on human heart G alpha h (hhG alpha h) has been identified that interacts with and stimulates PLC. Expressed mutants of hhG alpha h with deleted C-terminal regions lost the response to (-)-epinephrine and GTP and failed to coimmunoprecipitate PLC by the specific Gh7 alpha antibody. The interaction regions were further defined by studies with synthetic peptides of hhG alpha h and a chimera in which residues Val665-Lys672 of hhG alpha h were substituted with Ile707-Ser714 residues of human coagulation factor XIIIa. Thus, eight amino acid residues near the C terminus of hhG alpha h are critical for recognition and stimulation of PLC.