A WD-FYVE protein binds to the kinases Akt and PKCzeta/lambda

Biochem J. 2006 Oct 1;399(1):9-20. doi: 10.1042/BJ20060511.

Abstract

WD (tryptophan-aspartic acid dipeptide)-repeat proteins play a central role in signal transduction cascades by co-ordinating the interaction of key signalling molecules. We identified a novel propeller-FYVE [domain identified in Fab1p, YOTB, Vac1p and EEA1 (early endosome antigen 1)] protein, ProF, which is expressed in various cell lines and tissues and consists of seven WD-repeats and a FYVE domain. WD-repeat proteins offer a platform for protein-protein interactions by folding into a seven-bladed propeller-like structure, while the FYVE domain binds to phosphatidylinositol 3-phosphate present mainly on intracellular membranes. The ProF protein partially co-localizes with EEA1 on vesicular structures and binds to the protein kinases Akt and PKCzeta/lambda (protein kinase Czeta/lambda) via its WD-repeat propeller. ProF interacts more strongly with the kinases after hormonal stimulation. Endogenously expressed ProF and the two kinases interact in brain and in the preadipocyte cell line 3T3-L1, suggesting a role in secretory vesicular processes. In summary, we describe a new binding partner for kinases, located on vesicular structures in specialized cells, which may play a role for the spatial organization of signalling cascades.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / isolation & purification
  • Carrier Proteins / metabolism*
  • Cell Line
  • Chlorocebus aethiops
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Isoenzymes / metabolism*
  • Mice
  • Molecular Sequence Data
  • Oncogene Protein v-akt / metabolism*
  • Protein Conformation
  • Protein Kinase C / metabolism*
  • Protein Structure, Tertiary
  • Rats
  • Signal Transduction

Substances

  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Isoenzymes
  • ProF protein, mouse
  • WDFY2 protein, human
  • Oncogene Protein v-akt
  • protein kinase C zeta
  • Protein Kinase C
  • protein kinase C lambda

Associated data

  • GENBANK/AAL04162