RGSZ1, a G(z)-selective regulator of g protein signaling whose action is sensitive to the phosphorylation state of G(z)α

Abstract

Regulators of G protein signaling (RGS) are a family of proteins that attenuate the activity of the trimeric G proteins. RGS proteins act as GTPase-activating proteins (GAPs) for the α subunits of several trimeric G proteins, much like the GAPs that regulate the activity of monomeric G proteins such as Ras. RGS proteins have been cloned from many eukaryotes, and those whose biochemical activity has been characterized regulate the members of the G(i) family of G proteins; some forms can also act on G(q) proteins. In an ongoing effort to elucidate the role of G(z)α in cell signaling, the yeast two-hybrid system was employed to identify proteins that could interact with a mutationally activated form of G(z)α. A novel RGS, termed RGSZ1, was identified that is most closely related to two existing RGS proteins termed RetRGS1 and GAIP. Northern blot analysis revealed that expression of RGSZ1 was limited to brain, and expression was particularly high in the caudate nucleus. Biochemical characterization of recombinant RGSZ1 protein revealed that RGSZ1 was indeed a GAP and, most significantly, showed a marked preference for G(z)α over other members of the G(i)α family. Phosphorylation of G(z)α by protein kinase C, an event known to occur in cells and that was previously shown to influence α-βγ interactions of G(z), rendered the G protein much less susceptible to RGSZ1 action.