Identification of a GTPase activating protein specific for the heterotrimeric G protein, Gz

Gz is a member of the Gi family of trimeric G proteins whose precise signalling function has not been defined. It can be distinguished from other members of the family by several interesting biochemical properties of its alpha subunit, Gzalpha. One particularly intriguing property is its extremely slow GTPase activity; its kcat for GTP hydrolysis is as much as 200-fold less than other Galpha's. Since there is evidence that cellular factors can accelerate the GTPase activities of Galpha subunits, we have suspected that cells expressing Gzalpha may contain a GTPase-activating protein, or GAP, that would enhance its hydrolytic ability. Using purified Gzalpha-GTP as a substrate, we have identified and characterized such a GAP that acts on Gzalpha, which we have termed Gz-GAP. The protein responsible for this activity is specific for Gzalpha and is found in the membrane fraction of bovine brain and in several other tissues that express Gz. Since G protein effectors are in many cases capable of stimulating the GTPases rate of Galpha subunits, we speculate that a novel effector for Gz is responsible for the activity.