Our pervious data demonstrated that overexpression of HSG exhibits a profound anti-proliferative and proapoptotic effects in vivo and in vitro. To further confirm the role of HSG in controlling cell growth, we performed this study using primary human T-cells and B cell lymphoma cell line BJAB. We have observed that HSG plays an essential role in cell growth. HSG was down regulated in anti-CD3 and anti-CD28 activated T-cells, which was blocked by mTOR inhibitor Rapamycin, PI3K inhibitor Ly294002, Akt inhibitor A443654, and anti-IL2 antibody, but unaffected by cyclosporin A. Treatment of BJAB cells with rapamycin and A443654 resulted in growth suppression, and concomitant increase in HSG expression, Overexpression of HSG suppressed serum-evoked BJAB proliferation in culture. Knocked down of HSG in BJAB cells showed enhancement in cell growth. We have observed that the down regulation of HSG was regulated by Akt via proteosomal degradation. We have also observed that HSG interacts with Ras to inhibit Ras-Raf-MEK-ERK pathway. Currently, we are investigating whether HSG is a Ras effector molecule. We are also studying the status of HSG in proliferating T cells from young and old mice to determine whether HSG is involved in altered proliferative response of T cells from old mice.