scholarly journals Inactivation of the Tuberous Sclerosis Complex-1 and -2 Gene Products Occurs by Phosphoinositide 3-Kinase/Akt-dependent and -independent Phosphorylation of Tuberin

2003 ◽  
Vol 278 (39) ◽  
pp. 37288-37296 ◽  
Author(s):  
Andrew R. Tee ◽  
Rana Anjum ◽  
John Blenis
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Gene Products ◽  
Phosphoinositide 3 Kinase

United at last: the tuberous sclerosis complex gene products connect the phosphoinositide 3-kinase/Akt pathway to mammalian target of rapamycin (mTOR) signalling

2003 ◽  
Vol 31 (3) ◽  
pp. 573-578 ◽  
Author(s):  
B.D. Manning ◽  
L.C. Cantley
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Complex Disease ◽  
Mammalian Target Of Rapamycin ◽  
Pi3k Pathway ◽  
Target Of Rapamycin ◽  
Gene Products ◽  
Phosphoinositide 3 Kinase ◽  
The Many ◽  
Mtor Signalling

The molecular interplay between the phosphoinositide 3-kinase (PI3K) pathway and mammalian target of rapamycin (mTOR) signalling in the control of cell growth and proliferation has been the subject of much interest and debate amongst cell biologists. A recent escalation of research in this area has come from the discovery of the tuberous sclerosis complex gene products, tuberin and hamartin, as central regulators of mTOR activation. The PI3K effector Akt/protein kinase B has been found to directly phosphorylate tuberin and is thereby thought to activate mTOR through inhibition of the tuberin–hamartin complex. The many recent studies aimed at defining the molecular nature of this revamped PI3K/Akt/mTOR pathway are reviewed here. The collective data discussed have laid the groundwork for important new insights into the many cancers caused by aberrant PI3K activation and the clinically challenging tuberous sclerosis complex disease and have suggested a possible means of treatment for both.

scholarly journals Heterozygosity for the tuberous sclerosis complex (TSC) gene products results in increased astrocyte numbers and decreased p27-Kip1 expression in TSC2+/− cells

Oncogene ◽  
2002 ◽  
Vol 21 (25) ◽  
pp. 4050-4059 ◽  
Author(s):  
Erik J Uhlmann ◽  
Anthony J Apicelli ◽  
Rebecca L Baldwin ◽  
Stephen P Burke ◽  
M Livia Bajenaru ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Gene Products ◽  
P27 Kip1

Expression of the tuberous sclerosis complex gene products, hamartin and tuberin, in central nervous system tissues

2000 ◽  
Vol 99 (3) ◽  
pp. 223-230 ◽  
Author(s):  
D. H. Gutmann ◽  
Y. Zhang ◽  
M. J. Hasbani ◽  
M. P. Goldberg ◽  
T. L. Plank ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Gene Products

The tuberous sclerosis complex (TSC) pathway and mechanism of size control

2003 ◽  
Vol 31 (3) ◽  
pp. 584-586 ◽  
Author(s):  
C.J. Potter ◽  
L.G. Pedraza ◽  
H. Huang ◽  
T. Xu
Keyword(s):  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Insulin Signalling ◽  
Size Control ◽  
Genetic Screens ◽  
Tissue Size ◽  
Phosphoinositide 3 Kinase ◽  
Phosphatase And Tensin Homologue ◽  
Deficient Mice ◽  
Growth Constraint

We have identified three groups of growth-constraint genes using mosaic genetic screens in Drosophila melanogaster, including PTEN (phosphatase and tensin homologue deleted on chromosome 10), and the tuberous sclerosis complex (TSC) genes, Tsc1 and Tsc2. Our studies show that all three groups of genes participate in mechanisms that regulate organ and organism size in animals. We propose that mechanisms of organ size control are critical targets for diseases, such as tumorigenesis, which require an increase in tissue size and total mass, and for evolutionary events that alter the size of organisms. Using genetic and biochemical methods, we have shown that Tsc1 and Tsc2 function in the insulin/phosphoinositide 3-kinase (PI3K)/Akt pathway. We have shown that Akt regulates the Tsc1–Tsc2 complex by directly phosphorylating Tsc2. We have shown further that S6 kinase (S6K) is a downstream component of the PI3K/Akt/TSC pathway and reduction of S6K activity can block TSC defects. Recent studies from many laboratories have now confirmed our findings in mice, rats and human patients, and have shown that drugs that antagonize S6K activities, such as rapamycin, diminish tumours in TSC-deficient mice and rats. Clinical trials based on these findings have begun. Given that other components of the pathway, such as PTEN, are also mutated in a large number of cancer patients and that these components regulate intracellular insulin signalling, therapeutics based on the knowledge of the pathway could have effects beyond the TSC patient population.

Sign in / Sign up

Export Citation Format

Share Document