Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

The phosphatidylinositol 3-kinase/akt cassette regulates purine nucleotide synthesis

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Wang, W.
  • Fridman, A.
  • Blackledge, W.
  • Connelly, S.
  • Wilson, Ian
  • Pilz, R. B.
  • Boss, G. R.

publication date

  • February 2009

journal

  • Journal of Biological Chemistry  Journal

abstract

  • The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway is highly conserved throughout evolution and regulates cell size and survival and cell cycle progression. It regulates the latter by stimulating procession through G(1) and the G(1)/S phase transition. Entry into S phase requires an abundant supply of purine nucleotides, but the effect of the PI3K/Akt pathway on purine synthesis has not been studied. We now show that the PI3K/Akt cassette regulates both de novo and salvage purine nucleotide synthesis in insulin-responsive mouse mesenchymal cells. We found that serum and insulin stimulated de novo purine synthesis in serum-starved cells largely through PI3K/Akt signaling, and pharmacologic and genetic inhibition of PI3K/Akt reduced de novo synthesis by 75% in logarithmically growing cells. PI3K/Akt regulated early steps of de novo synthesis by modulating phosphoribosylpyrophosphate production by the non-oxidative pentose phosphate pathway and late steps by modulating activity of the bifunctional enzyme aminoimidazole-carboxamide ribonucleotide transformylase IMP cyclohydrolase, an enzyme not previously known to be regulated. The effects of PI3K/Akt on purine nucleotide salvage were likely through regulating phosphoribosylpyrophosphate availability. These studies define a new mechanism whereby the PI3K/Akt cassette functions as a master regulator of cellular metabolism and a key player in oncogenesis.

subject areas

  • Animals
  • Cell Line
  • Cell Transformation, Neoplastic
  • Evolution, Molecular
  • G1 Phase
  • Humans
  • Insulin
  • Mice
  • Mice, Mutant Strains
  • Nucleotide Deaminases
  • Pentose Phosphate Pathway
  • Phosphatidylinositol 3-Kinases
  • Phosphoribosylaminoimidazolecarboxamide Formyltransferase
  • Proto-Oncogene Proteins c-akt
  • Purine Nucleotides
  • S Phase
  • Signal Transduction
scroll to property group menus

Identity

PubMed Central ID

  • PMC2635033

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M806707200

PubMed ID

  • 19068483
scroll to property group menus

Additional Document Info

start page

  • 3521

end page

  • 3528

volume

  • 284

issue

  • 6

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support