WD-repeat-propeller-FYVE protein, ProF, binds VAMP2 and protein kinase Czeta

FEBS J. 2007 Mar;274(6):1552-66. doi: 10.1111/j.1742-4658.2007.05702.x.


We have recently identified a protein, consisting of seven WD repeats, presumably forming a beta-propeller, and a domain identified in Fab1p, YOTB, VAC1p, and EEA1 (FYVE) domain, ProF. The FYVE domain targets the protein to vesicular membranes, while the WD repeats allow binding of the activated kinases Akt and protein kinase (PK)Czeta. Here, we describe the vesicle-associated membrane protein 2 (VAMP2) as interaction partner of ProF. The interaction is demonstrated with overexpressed and endogenous proteins in mammalian cells. ProF and VAMP2 partially colocalize on vesicular structures with PKCzeta and the proteins form a ternary complex. VAMP2 can be phosphorylated by activated PKCzeta in vitro and the presence of ProF increases the PKCzeta-dependent phosphorylation of VAMP2 in vitro. ProF is an adaptor protein that brings together a kinase with its substrate. VAMP2 is known to regulate docking and fusion of vesicles and to play a role in targeting vesicles to the plasma membrane. The complex may be involved in vesicle cycling in various secretory pathways.

MeSH terms

  • 3T3 Cells
  • Animals
  • COS Cells
  • Carrier Proteins / metabolism*
  • Chlorocebus aethiops
  • Humans
  • Immunoprecipitation
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Microscopy, Confocal
  • Phosphorylation
  • Protein Binding
  • Protein Kinase C / metabolism*
  • Substrate Specificity
  • Two-Hybrid System Techniques
  • Vesicle-Associated Membrane Protein 2 / metabolism*


  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • VAMP2 protein, human
  • Vesicle-Associated Membrane Protein 2
  • WDFY2 protein, human
  • protein kinase C zeta
  • Protein Kinase C