Identification of nucleolin as new ErbB receptors- interacting protein.
BACKGROUND
The ErbB receptor tyrosine kinases are major contributors to malignant transformation. These receptors are frequently overexpressed in a variety of human carcinomas. The role of the ErbB receptors and their ligands in carcinomas and the mechanism by which their overexpression leads to cancer development is still unclear. Ligand binding to specific ErbB receptor is followed by receptor dimerization, phosphorylation and recruitment of SH2 containing cytoplasmic proteins, which initiate the cascade of signaling events. Nevertheless, increasing data suggest that there are non-phosphorylated receptor-substrate interactions that may affect ErbB-mediated responses.


RESULTS
In the present study, using GST-ErbB4 fusion protein pull down assay and mass spectroscopic analysis, we have found the ErbB receptors interact with nucleolin via their cytoplasmic tail. Nucleolin is a ubiquitous, nonhistone, nucleolar, multifunctional phosphoprotein that is also overexpressed in cancer cells. Our results demonstrate that overexpression of ErbB1 and nucleolin may lead to receptor dimerization, phosphorylation and to anchorage independent growth.


CONCLUSIONS
The oncogenic potential of ErbB depends on receptor levels and activation. Our results suggest that nucleolin may affect ErbB dimerization and activation leading to enhanced cell growth.
Department of Neurobiology, Tel-Aviv University, Ramat-Aviv, Israel.
Ayelet
A
Di Segni
Keren
K
Farin
Ronit
R
Pinkas-Kramarski
D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002460:Cell Line; D017931:DNA Primers; D019281:Dimerization; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D000097796:Nucleolin
D017931:DNA Primers; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000097796:Nucleolin