Anti-Human Tuberous Sclerosis Complex 2 (CT) (TSC2) (T293-GRP)

Tuberous sclerosis complex (TSC) is an autosomal dominant tumor syndrome caused by mutations in either of the TSC1 or TSC2 tumor suppressor genes. The products of these genes form a protein complex that indirectly decreases the signaling of the mammalian Target of Rapamycin (TOR), an evolutionarily conserved serine/threonine kinase that regulates cell growth and cell cycle through its ability to integrate signals from nutrient levels and growth factors (reviewed in 1,2). TOR activity is stimulated by Rheb, a member of the Ras superfamily of G-proteins, when the GTP/GDP ratio bound to Rheb is high.3 Immunoprecipitated TSC1/TSC2 has been shown to stimulate Rheb GTPase activity in vitro,4 suggesting that the TSC1/TSC2 complex decreases the ability of Rheb to stimulate TOR activity. This is supported by experiments showing that overexpression of TSC1 and TSC2 results in a significant decrease in the GTP/GDP ratio bound to Rheb and the inhibition of cell growth.4 At least three isoforms of TSC2 exist.