Proliferation and differentiation of PC12 cells were affected by p21ras GTPase activating proteins and its deletion mutant proteins.

In this study, a mammalian expression vector containing cDNA of human GAP (p120GAP) or its deletion mutant was transfected into PC12 cells. The deletion mutant peptide has SH2 and SH3 domains, but no GTPase activating domain. Cells stably overexpressing intact p120GAP showed enhanced proliferation, demonstrated by 5-bromo-2'-deoxyuridine labeling and cell cycle analysis. On the other hand, in cells expressing the deletion mutant GAP, differentiation induced by NGF was potentiated, as demonstrated by enhanced acetylcholinesterase activity and induction of neurofilament proteins.