IDENTIFICATION OF A GTPASE-ACTIVATING PROTEIN-SPECIFIC FOR THE HETEROTRIMERIC G-PROTEIN, G(Z)

G(z) is a member of the G(i) family of trimeric G proteins whose preci se signalling function has not been defined. It can be distinguished f rom other members of the family by several interesting biochemical pro perties of its alpha subunit, G(z alpha). One particularly intriguing property is its extremely slow GTPase activity; its k(cat) for GTP hyd rolysis is as much as 200-fold less than other G(alpha)'s. Since there is evidence that cellular factors can accelerate the GTPase activitie s of G(alpha) subunits, we have suspected that cells expressing G(z al pha) may contain a GTPase-activating protein, or GAP, that would enhan ce its hydrolytic ability. Using purified G(z alpha)-GTP as a substrat e, we have identified and characterized such a GAP that acts on G(z al pha), which we have termed G(z)-GAP. The protein responsible for this activity is specific for G(z alpha) and is found in the membrane fract ion of bovine brain and in several other tissues that express G(z). Si nce G protein effecters are in many cases capable of stimulating the G TPases rate of G(alpha) subunits, we speculate that a novel effector f or G(z) is responsible for the activity. (C) 1998 Elsevier Science Inc .