G _h : a GTP-Binding Protein with Transglutaminase Activity and Receptor Signaling Function

TLDR

α1‑adrenergic receptors activate phospholipase C by coupling to large Gαh GTP‑binding proteins. Rat liver Gαh functions as a tissue transglutaminase type II whose activity is inhibited by GTP analogs or α1‑adrenergic receptor activation, and it mediates receptor‑stimulated phospholipase C activity, illustrating that Gαh can switch from transglutamination to signaling roles.

Abstract

The α 1 -adrenergic receptors activate a phospholipase C enzyme by coupling to members of the large molecular size (approximately 74 to 80 kilodaltons) Gα h family of guanosine triphosphate (GTP)-binding proteins. Rat liver Gα h is now shown to be a tissue transglutaminase type II (TGase II). The transglutaminase activity of rat liver TGase II expressed in COS-1 cells was inhibited by the nonhydrolyzable GTP analog guanosine 5′- O -(3-thiotriphosphate) or by α 1 -adrenergic receptor activation. Rat liver TGase II also mediated α 1 -adrenergic receptor stimulation of phospholipase C activity. Thus, Gα h represents a new class of GTP-binding proteins that participate in receptor signaling and may be a component of a complex regulatory network in which receptor-stimulated GTP binding switches the function of Gα h from transglutamination to receptor signaling.