A human phosphatidylinositol 3-kinase complex related to the yeast Vps34p-Vps15p protein sorting system

EMBO J. 1995 Jul 17;14(14):3339-48.

Abstract

Phosphoinositide (PI) 3-kinases have been characterized as enzymes involved in receptor signal transduction in mammalian cells and in a complex which mediates protein trafficking in yeast. PI 3-kinases linked to receptors with intrinsic or associated tyrosine kinase activity are heterodimeric proteins, consisting of p85 adaptor and p110 catalytic subunits, which can generate the 3-phosphorylated forms of phosphatidylinositol (PtdIns), PtdIns4P and PtdIns(4,5)P2 as potential second messengers. Yeast Vps34p kinase, however, has a substrate specificity restricted to PtdIns and is a PtdIns 3-kinase. Here the molecular characterization of a new human PtdIns 3-kinase with extensive sequence homology to Vps34p is described. PtdIns 3-kinase does not associate with p85 and phosphorylates PtdIns, but not PtdIns4P or PtdIns(4,5)P2. In vivo PtdIns 3-kinase is in a complex with a cellular protein of 150 kDa, as detected by immunoprecipitation from human cells. Protein sequence analysis and cDNA cloning show that this 150 kDa protein is highly homologous to Vps15p, a 160 kDa protein serine/threonine kinase associated with yeast Vps34p. These results suggest that the major components of the yeast Vps intracellular trafficking complex are conserved in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cell Line
  • Cloning, Molecular
  • Conserved Sequence
  • DNA
  • Endosomal Sorting Complexes Required for Transport
  • Humans
  • Molecular Sequence Data
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor) / chemistry
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae Proteins
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Vacuolar Sorting Protein VPS15

Substances

  • Endosomal Sorting Complexes Required for Transport
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • DNA
  • Protein Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • p150 protein kinase
  • PIK3R4 protein, human
  • Protein-Serine-Threonine Kinases
  • VPS15 protein, S cerevisiae
  • Vacuolar Sorting Protein VPS15

Associated data

  • GENBANK/Z46973