Interaction between tyrosine kinase Etk and a RUN domain- and FYVE domain-containing protein RUFY1. A possible role of ETK in regulation of vesicle trafficking

J Biol Chem. 2002 Aug 16;277(33):30219-26. doi: 10.1074/jbc.M111933200. Epub 2002 Mar 4.


Etk/BMX tyrosine kinase is involved in regulation of various cellular processes including proliferation, differentiation, motility, and apoptosis. Through a yeast two-hybrid screening for the effectors of Etk, a new gene family designated as RUFY was identified. The RUFY gene family (RUFY1 and RUFY2) contains an N-terminal RUN domain and a C-terminal FYVE domain with two coiled-coil domains in-between. They appear to be homologues of a recently identified mouse Rabip4 (Cormant, M., Mari, M., Galmiche, A., Hofman, P., and Le Marchand-Brustel, Y. (2001) Proc. Natl. Acad. Sci. U. S. A. 98, 1637-1642). RUFY proteins are localized predominantly to endosomes as evidenced by their co-localization with early endosome antigen marker (EEA1). Etk interacts with RUFY1 through its SH3 and SH2 domains. RUFY1 is tyrosine-phosphorylated and appears to be a substrate of Etk. The RUFY1 mutant lacking the phosphorylation sites failed to go to the endosomes. Furthermore, overexpression of Etk in COS-1 and B82L cells resulted in increased plasma membrane localization of the epidermal growth factor receptor and delayed its induced endocytosis in COS-1 cells. The effects of Etk were blocked by the FYVE domain of RUFY1. Interestingly, the FYVE domain of RUFY1 is targeted to the plasma membrane through an interaction between its proline-rich motif and the SH3 domain of Etk or possibly some other membrane-associated SH3 domain-containing protein(s), whereas the lipid binding activity of the FYVE domain is not required. Our data suggest that Etk may be involved in regulation of endocytosis through its interaction with an endosomal protein RUFY1.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • DNA, Complementary
  • Endocytosis
  • ErbB Receptors / metabolism
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Molecular Sequence Data
  • Nuclear Proteins
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoproteins / chemistry
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein-Tyrosine Kinases / metabolism*
  • Protein-Tyrosine Kinases / physiology
  • Sequence Homology, Amino Acid
  • Two-Hybrid System Techniques


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA, Complementary
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • RUFY1 protein, human
  • RUFY2 protein, human
  • BMX protein, human
  • Bmx protein, mouse
  • ErbB Receptors
  • Protein-Tyrosine Kinases