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

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

  • July 1, 2002

Research

keywords

  • Phosphatidylinositol 3-Kinases
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Signal Transduction

Identity

Scopus Document Identifier

  • 0036342294

Digital Object Identifier (DOI)

  • 10.1016/s1097-2765(02)00568-3

PubMed ID

  • 12150915

Additional Document Info

volume

  • 10

issue

  • 1