Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/Akt pathway Academic Article uri icon

Overview

MeSH Major

  • Arthroplasty, Replacement
  • Intervertebral Disc
  • Lumbar Vertebrae
  • Spinal Diseases

abstract

  • The S/T-protein kinases activated by phosphoinositide 3-kinase (PI3K) regulate a myriad of cellular processes. Here, we show that an approach using a combination of biochemistry and bioinformatics can identify substrates of these kinases. This approach identifies the tuberous sclerosis complex-2 gene product, tuberin, as a potential target of Akt/PKB. We demonstrate that, upon activation of PI3K, tuberin is phosphorylated on consensus recognition sites for PI3K-dependent S/T kinases. Moreover, Akt/PKB can phosphorylate tuberin in vitro and in vivo. We also show that S939 and T1462 of tuberin are PI3K-regulated phosphorylation sites and that T1462 is constitutively phosphorylated in PTEN(-/-) tumor-derived cell lines. Finally, we find that a tuberin mutant lacking the major PI3K-dependent phosphorylation sites can block the activation of S6K1, suggesting a means by which the PI3K-Akt pathway regulates S6K1 activity.

publication date

  • August 23, 2002

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1016/S1097-2765(02)00568-3

Additional Document Info

start page

  • 151

end page

  • 62

volume

  • 10

number

  • 1