An essential role for phosphatidylinositol transfer protein in phospholipase C-mediated inositol lipid signaling

Cell. 1993 Sep 10;74(5):919-28. doi: 10.1016/0092-8674(93)90471-2.

Abstract

Transmembrane signaling by the phospholipase C-beta (PLC-beta) pathway is known to require at least three components: the receptor, the G protein, and the PLC. Recent studies have indicated that if the cytosol is allowed to leak out of HL60 cells, then G protein-stimulated PLC activity is greatly diminished, indicating an essential role for a cytosolic component(s). We now report the complete purification of one component based on its ability to reconstitute GTP gamma S-mediated PLC activity and identify it as the phosphatidylinositol transfer protein (PI-TP). Based on the in vitro effects of PI-TP, we surmise that it is involved in transporting PI from intracellular compartments for conversion to PI bisphosphate (PIP2) prior to hydrolysis by PLC-beta 2/PLC-beta 3, the endogenous PLC isoforms present in these cells.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / chemistry
  • Carrier Proteins / isolation & purification
  • Carrier Proteins / metabolism*
  • Cell Membrane / metabolism
  • GTP-Binding Proteins / metabolism*
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
  • Humans
  • Immunoblotting
  • Kinetics
  • Leukemia, Promyelocytic, Acute
  • Membrane Proteins*
  • Molecular Sequence Data
  • Phosphatidylinositols / metabolism*
  • Phospholipid Transfer Proteins
  • Rats
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • Tumor Cells, Cultured
  • Type C Phospholipases / chemistry
  • Type C Phospholipases / isolation & purification
  • Type C Phospholipases / metabolism*

Substances

  • Carrier Proteins
  • Membrane Proteins
  • Phosphatidylinositols
  • Phospholipid Transfer Proteins
  • SEC24 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Type C Phospholipases
  • GTP-Binding Proteins