INTERACTION SITE OF GTP-BINDING G(H) (TRANSGLUTAMINASE-II) WITH PHOSPHOLIPASE-C

The GTP binding G alpha(h) (transglutaminase II) mediates the alpha(1B )-adrenoreceptor signal to a 69-kDa phospholipase C (PLC). Thus, G alp ha(h) possesses both GTPase and transglutaminase activities with a sig nal transfer role. The recognition sites of this unique GTP binding pr otein for either the receptor or the effector are completely unknown. A site on human heart G alpha(h) (hhG alpha(h)) has been identified th at 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 G(h7 al pha) antibody. The interaction regions were further defined by studies with synthetic peptides of hhG alpha(h) and a chimera in which residu es VaL(665)-Lys(672) of hhG alpha(h) were substituted with Ile(707)-Se r(714) residues of human coagulation factor XIIIa. Thus, eight amino a cid residues near the C terminus of hhG alpha(h) are critical for reco gnition and stimulation of PLC.