DIFFERENTIAL CONTRIBUTION OF M(R) 120 KDA RASGTPASE-ACTIVATING PROTEIN AND NEUROFIBROMATOSIS TYPE-1 GENE-PRODUCT DURING THE TRANSITION FROM GROWTH-PHASE TO ARRESTED STATE IN HUMAN FIBROBLASTS ACCOMPANIED BY A UNIQUE RASGTPASE-ACTIVATING ACTIVITY

Using octyl glucoside-solubilized cell extracts from human fibroblasts during growth phase to G0/G1 arrest state, we found that while the number of M(r) 120 kDa rasGTPase-activating protein (p120GAP) molecules per cell decreases to half its original levels, the amount of neurofibromatosis type 1 gene product (NF1, neurofibromin) remains constant during the transition. The contribution of p 120GAP to the total rasGTPase-activating (rasGA) activity in growing cells was found to be larger than that observed in arrested cells (84% vs 53%). On the other hand, NF1 contributes less than 15% of the total rasGA activity in either extract. These results indicate that the qualitative changes occur in the contributors to rasGA activity during transition. They also suggest that a unique rasGA activity exists in the arrested cells, which was obtained separatedly from both p120GAP and NF1 by heparin-Sepharose column chromatography.