CFBP is a novel tyrosine-phosphorylated protein that might function as a regulator of CIN85/CD2AP.
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.
Konishi
Hiroaki
H
Institute for Enzyme Research, University of Tokushima, Tokushima 770-8503, Japan and Harima Institute at SPring-8, RIKEN, Hyogo 679-5148, Japan. konishi@ier.tokushima-u.ac.jp
Tashiro
Kyoko
K
Murata
Yasunobu
Y
Nabeshi
Hiromi
H
Yamauchi
Emiko
E
Taniguchi
Hisaaki
H
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry / Q000502:physiology*; D010766:Phosphorylation; D014443:Tyrosine / Q000737:chemistry*
D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C514895:MVB12A protein, human; D010750:Phosphoproteins; C433810:SH3KBP1 protein, human; D014443:Tyrosine; D066246:ErbB Receptors