CFBP is a novel tyrosine-phosphorylated protein that might function as a regulator of CIN85/CD2AP

J Biol Chem. 2006 Sep 29;281(39):28919-31. doi: 10.1074/jbc.M605693200. Epub 2006 Aug 7.

Abstract

To decipher the global network of the epidermal growth factor (EGF) receptor-mediated signaling pathway, a large scale proteomic analysis of tyrosine-phosphorylated proteins was conducted. Here, we focus on characterizing a novel protein, CFBP (CIN85/CD2AP family binding protein), identified in the study. CFBP was found to be phosphorylated at tyrosine 204 upon EGF stimulation, and the CIN85/CD2AP family was identified as a binding partner. A proline-rich motif of CFBP is recognized by one of the three Src-homology 3 domains of CIN85/CD2AP, and the affinity of the interaction is regulated by the tyrosine phosphorylation of CFBP. They co-localize in actinenriched structures, and overexpression of CFBP induced morphological changes with actin reorganization. Furthermore, CFBP accelerated the EGF receptor's down-regulation by facilitating the recruitment of Cbl to the CD2AP/CIN85 complex. Two spliced variants of CFBP lacking either exon 5 or 8 are also expressed, and the variant lacking exon 5 without the proline-rich motif lacks the ability to bind to the CIN85/CD2AP family. The CFBP protein seems to play a key role in the ligand-mediated internalization and down-regulation of the EGF receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / physiology*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • COS Cells
  • Carrier Proteins / chemistry
  • Carrier Proteins / physiology*
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Cytoskeletal Proteins / physiology*
  • ErbB Receptors / metabolism
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Phosphoproteins / chemistry
  • Phosphoproteins / physiology*
  • Phosphorylation
  • Tyrosine / chemistry*

Substances

  • Adaptor Proteins, Signal Transducing
  • CD2-associated protein
  • Carrier Proteins
  • Cytoskeletal Proteins
  • MVB12A protein, human
  • Phosphoproteins
  • SH3KBP1 protein, human
  • Tyrosine
  • ErbB Receptors