Mouse p170 is a novel phosphatidylinositol 3-kinase containing a C2 domain

J Biol Chem. 1996 Jun 7;271(23):13304-7. doi: 10.1074/jbc.271.23.13304.

Abstract

Phosphatidylinositol (PI) 3-kinases catalyze the formation of 3'-phosphoinositides, which appear to promote cellular responses to growth factors and such membrane trafficking events as insulin-stimulated translocation of intracellular glucose transporters. We report here the cloning of a novel PI 3-kinase, p170, from cDNA of insulin-sensitive mouse 3T3-L1 adipocytes. Mouse p170 utilizes PI and to a limited extent PI 4-P as substrates, in contrast to the PI-specific yeast VPS34 homolog PtdIns 3-kinase and the p110 PI 3-kinases, which phosphorylate PI, PI 4-P, and PI 4,5-P2. Mouse p170 is also distinct from PtdIns 3-kinase or the p110 PI 3-kinases in exhibiting a 10-fold lower sensitivity to wortmannin. Unique structural elements of p170 include C-terminal sequences strikingly similar to the phosphoinositide-binding C2 domain of protein kinase C isoforms, synaptotagmins, and other proteins. These features of mouse p170 are shared with a recently cloned Drosophila PI 3-kinase, DmPI3K_68D. Together, these proteins define a new class of PI 3-kinase likely influenced by cellular regulators distinct from those acting upon p110- or VPS34-like PI 3-kinases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Androstadienes / pharmacology
  • Animals
  • Base Sequence
  • Cloning, Molecular
  • DNA Primers / genetics
  • DNA, Complementary / genetics
  • Drosophila
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Mice
  • Molecular Sequence Data
  • Molecular Structure
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor) / chemistry*
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Wortmannin

Substances

  • Androstadienes
  • DNA Primers
  • DNA, Complementary
  • Enzyme Inhibitors
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • Wortmannin

Associated data

  • GENBANK/U55772